Event-based control of a lumen traveling device

ABSTRACT

Methods of controlling the operation of a device traveling in a body tube tree, including selecting a direction of travel based on information relating to a previous event associated with a possible direction of travel, implemented with a control system located partially or fully on the lumen traveling device. Various actions can be performed by the device for, e.g., medical or therapeutic purposes. Machine-readable media including instructions for performing the methods are also described.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to and claims the benefit of theearliest available effective filing date(s) from the following listedapplication(s) (the “Related Applications”) (e.g., claims earliestavailable priority dates for other than provisional patent applicationsor claims benefits under 35 USC §119(e) for provisional patentapplications, for any and all parent, grandparent, great-grandparent,etc. applications of the Related Application(s)). All subject matter ofthe Related Applications and of any and all parent, grandparent,great-grandparent, etc. applications of the Related Applications isincorporated herein by reference to the extent such subject matter isnot inconsistent herewith.

Related Applications:

-   -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/403,230, titled LUMENALLY-ACTIVE        DEVICE, naming Bran Ferren, W. Daniel Hillis, Roderick A. Hyde,        Muriel Y. Ishikawa, Edward K. Y. Jung, Nathan P. Myhrvold,        Elizabeth A. Sweeney, Clarence T. Tegreene, Richa Wilson,        Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed        12 Apr. 2006, which is currently co-pending, or is an        application of which a currently co-pending application is        entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/417,898, titled CONTROLLABLE        RELEASE NASAL SYSTEM, naming W. Daniel Hillis, Roderick A. Hyde,        Muriel Y. Ishikawa, Elizabeth A. Sweeney, Clarence T. Tegreene,        Richa Wilson, Lowell L. Wood, Jr., and Victoria Y. H. Wood as        inventors, filed 4 May 2006, which is currently co-pending, or        is an application of which a currently co-pending application is        entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/478,368, titled LUMENALLY-ACTIVE        DEVICE, naming Bran Ferren, W. Daniel Hillis, Roderick A. Hyde,        Muriel Y. Ishikawa, Edward K. Y. Jung, Nathan P. Myhrvold,        Elizabeth A. Sweeney, Clarence T. Tegreene, Richa Wilson,        Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed        28 Jun. 2006, which is currently co-pending, or is an        application of which a currently co-pending application is        entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/485,619, titled CONTROLLABLE        RELEASE NASAL SYSTEM, naming W. Daniel Hillis, Roderick A. Hyde,        Muriel Y. Ishikawa, Elizabeth A. Sweeney, Clarence T. Tegreene,        Richa Wilson, Lowell L. Wood, Jr., and Victoria Y. H. Wood as        inventors, filed 11 Jul. 2006, which is currently co-pending, or        is an application of which a currently co-pending application is        entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/645,358, titled LUMEN-TRAVELING        DEVICE, naming Bran Ferren, W. Daniel Hillis, Roderick A. Hyde,        Muriel Y. Ishikawa, Edward K. Y. Jung, Eric C. Leuthardt,        Nathan P. Myhrvold, Elizabeth A. Sweeney, Clarence T. Tegreene,        Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed        21 Dec. 2006, which is currently co-pending, or is an        application of which a currently co-pending application is        entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/651,946, titled LUMEN-TRAVELING        DELIVERY DEVICE, naming Bran Ferren, W. Daniel Hillis,        Roderick A. Hyde, Muriel Y. Ishikawa, Edward K. Y. Jung, Eric C.        Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney, Clarence T.        Tegreene, Lowell L. Wood, Jr., and Victoria Y. H. Wood as        inventors, filed 9 Jan. 2007, which is currently co-pending, or        is an application of which a currently co-pending application is        entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/725,982, titled LUMEN-TRAVELING        BIOLOGICAL INTERFACE DEVICE, naming Bran Ferren, W. Daniel        Hillis, Roderick A. Hyde, Muriel Y. Ishikawa, Edward K. Y. Jung,        Eric C. Leuthardt, Nathan P. Myhrvold, Clarence T. Tegreene,        Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed        19 Mar. 2007, which is currently co-pending, or is an        application of which a currently co-pending application is        entitled to the benefit of the filing date, and which is a        continuation-in-part of U.S. patent application Ser. No.        11/645,357, titled LUMEN-TRAVELING DEVICE, naming Bran        Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y. Ishikawa,        Edward K. Y. Jung, Eric C. Leuthardt, Nathan P. Myhrvold,        Elizabeth A. Sweeney, Clarence T. Tegreene, Lowell L. Wood, Jr.,        and Victoria Y. H. Wood as inventors, filed 21 Dec. 2006, now        U.S. Pat. No. 7,857,767 issued 28 Dec. 2010, which is currently        co-pending, or is an application of which a currently co-pending        application is entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/726,025, titled        BIOELECTROMAGNETIC INTERFACE SYSTEM, naming Bran Ferren, W.        Daniel Hillis, Roderick A. Hyde, Muriel Y. Ishikawa,        Edward K. Y. Jung, Eric C. Leuthardt, Nathan P. Myhrvold,        Clarence T. Tegreene, Lowell L. Wood, Jr., and Victoria Y. H.        Wood as inventors, filed 19 Mar. 2007, which is currently        co-pending, or is an application of which a currently co-pending        application is entitled to the benefit of the filing date, and        which is a continuation-in-part of U.S. patent application Ser.        No. 11/645,357, titled LUMEN-TRAVELING DEVICE, naming Bran        Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y. Ishikawa,        Edward K. Y. Jung, Eric C. Leuthardt, Nathan P. Myhrvold,        Elizabeth A. Sweeney, Clarence T. Tegreene, Lowell L. Wood, Jr.,        and Victoria Y. H. Wood as inventors, filed 21 Dec. 2006, now        U.S. Pat. No. 7,857,767 issued 28 Dec. 2010, which is currently        co-pending, or is an application of which a currently co-pending        application is entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 11/726,031, titled LUMEN-TRAVELING        BIOLOGICAL INTERFACE DEVICE AND METHOD OF USE, naming Bran        Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y. Ishikawa,        Edward K. Y. Jung, Eric C. Leuthardt, Nathan P. Myhrvold,        Clarence T. Tegreene, Lowell L. Wood, Jr., and Victoria Y. H.        Wood as inventors, filed 19 Mar. 2007, which is currently        co-pending, or is an application of which a currently co-pending        application is entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 12/319,882, titled LUMEN-TRAVELING        BIOLOGICAL INTERFACE DEVICE AND METHOD OF USE, naming Bran        Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y. Ishikawa,        Edward K. Y. Jung, Eric C. Leuthardt, Nathan P. Myhrvold,        Clarence T. Tegreene, Lowell L. Wood, Jr., and Victoria Y. H.        Wood as inventors, filed 12 Jan. 2009, which is currently        co-pending, or is an application of which a currently co-pending        application is entitled to the benefit of the filing date, and        which is a divisional of U.S. patent application Ser. No.        11/726,031, titled LUMEN-TRAVELING BIOLOGICAL INTERFACE DEVICE        AND METHOD OF USE, naming Bran Ferren, W. Daniel Hillis,        Roderick A. Hyde, Muriel Y. Ishikawa, Edward K. Y. Jung, Eric C.        Leuthardt, Nathan P. Myhrvold, Clarence T. Tegreene, Lowell L.        Wood, Jr., and Victoria Y. H. Wood as inventors, filed 19 Mar.        2007, which is currently co-pending, or is an application of        which a currently co-pending application is entitled to the        benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 12/319,881, titled LUMEN-TRAVELING        BIOLOGICAL INTERFACE DEVICE AND METHOD OF USE, naming Bran        Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y. Ishikawa,        Edward K. Y. Jung, Eric C. Leuthardt, Nathan P. Myhrvold,        Clarence T. Tegreene, Lowell L. Wood, Jr., and Victoria Y. H.        Wood as inventors, filed 12 Jan. 2009, which is currently        co-pending, or is an application of which a currently co-pending        application is entitled to the benefit of the filing date, and        which is a divisional of U.S. patent application Ser. No.        11/726,031, titled LUMEN-TRAVELING BIOLOGICAL INTERFACE DEVICE        AND METHOD OF USE, naming Bran Ferren, W. Daniel Hillis,        Roderick A. Hyde, Muriel Y. Ishikawa, Edward K. Y. Jung, Eric C.        Leuthardt, Nathan P. Myhrvold, Clarence T. Tegreene, Lowell L.        Wood, Jr., and Victoria Y. H. Wood as inventors, filed 19 Mar.        2007, which is currently co-pending, or is an application of        which a currently co-pending application is entitled to the        benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. To be assigned, titled CONTROL OF A        LUMEN TRAVELING DEVICE IN A BODY TUBE TREE, naming Bran        Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y. Ishikawa,        Edward K. Y. Jung, Eric C. Leuthardt, Nathan P. Myhrvold,        Thomas J. Nugent, Jr., Elizabeth A. Sweeney, Clarence T.        Tegreene, Lowell L. Wood, Jr., and Victoria Y. H. Wood as        inventors, filed substantially contemporaneously herewith, which        is currently co-pending, or is an application of which a        currently co-pending application is entitled to the benefit of        the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. To be assigned, titled TEMPORAL        CONTROL OF A LUMEN TRAVELING DEVICE IN A BODY TUBE TREE, naming        Bran Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y.        Ishikawa, Edward K. Y. Jung, Eric C. Leuthardt, Nathan P.        Myhrvold, Thomas J. Nugent, Jr., Elizabeth A. Sweeney,        Clarence T. Tegreene, Lowell L. Wood, Jr., and Victoria Y. H.        Wood as inventors, filed substantially contemporaneously        herewith, which is currently co-pending, or is an application of        which a currently co-pending application is entitled to the        benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. To be assigned, titled PATH        SELECTION BY A LUMEN TRAVELING DEVICE IN A BODY TUBE TREE BASED        ON PREVIOUS PATH, naming Bran Ferren, W. Daniel Hillis,        Roderick A. Hyde, Muriel Y. Ishikawa, Edward K. Y. Jung, Eric C.        Leuthardt, Nathan P. Myhrvold, Thomas J. Nugent, Jr.,        Elizabeth A. Sweeney, Clarence T. Tegreene, Lowell L. Wood, Jr.,        and Victoria Y. H. Wood as inventors, filed substantially        contemporaneously herewith, which is currently co-pending, or is        an application of which a currently co-pending application is        entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. To be assigned, titled        PARAMETER-BASED NAVIGATION BY A LUMEN TRAVELING DEVICE, naming        Bran Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y.        Ishikawa, Edward K. Y. Jung, Eric C. Leuthardt, Nathan P.        Myhrvold, Thomas J. Nugent, Jr., Elizabeth A. Sweeney,        Clarence T. Tegreene, Lowell L. Wood, Jr., and Victoria Y. H.        Wood as inventors, filed substantially contemporaneously        herewith, which is currently co-pending, or is an application of        which a currently co-pending application is entitled to the        benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. To be assigned, titled NAVIGATION OF        A LUMEN TRAVELING DEVICE TOWARD A TARGET, naming Bran Ferren, W.        Daniel Hillis, Roderick A. Hyde, Muriel Y. Ishikawa,        Edward K. Y. Jung, Eric C. Leuthardt, Nathan P. Myhrvold,        Thomas J. Nugent, Jr., Elizabeth A. Sweeney, Clarence T.        Tegreene, Lowell L. Wood, Jr., and Victoria Y. H. Wood as        inventors, filed substantially contemporaneously herewith, which        is currently co-pending, or is an application of which a        currently co-pending application is entitled to the benefit of        the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. To be assigned, titled MAP-BASED        NAVIGATION OF A BODY TUBE TREE BY A LUMEN TRAVELING DEVICE,        naming Bran Ferren, W. Daniel Hillis, Roderick A. Hyde,        Muriel Y. Ishikawa, Edward K. Y. Jung, Eric C. Leuthardt,        Nathan P. Myhrvold, Thomas J. Nugent, Jr., Elizabeth A. Sweeney,        Clarence T. Tegreene, Lowell L. Wood, Jr., and Victoria Y. H.        Wood as inventors, filed substantially contemporaneously        herewith, which is currently co-pending, or is an application of        which a currently co-pending application is entitled to the        benefit of the filing date.

The United States Patent Office (USPTO) has published a notice to theeffect that the USPTO's computer programs require that patent applicantsreference both a serial number and indicate whether an application is acontinuation or continuation-in-part. Stephen G. Kunin, Benefit ofPrior-Filed Application, USPTO Official Gazette Mar. 18, 2003, availableat http://www.uspto.gov/web/offices/com/sol/og/2003/week11/patbene.htm.The present Applicant Entity (hereinafter “Applicant”) has providedabove a specific reference to the application(s) from which priority isbeing claimed as recited by statute. Applicant understands that thestatute is unambiguous in its specific reference language and does notrequire either a serial number or any characterization, such as“continuation” or “continuation-in-part,” for claiming priority to U.S.patent applications. Notwithstanding the foregoing, Applicantunderstands that the USPTO's computer programs have certain data entryrequirements, and hence Applicant is designating the present applicationas a continuation-in-part of its parent applications as set forth above,but expressly points out that such designations are not to be construedin any way as any type of commentary and/or admission as to whether ornot the present application contains any new matter in addition to thematter of its parent application(s).

BACKGROUND

Devices and systems for use in various body lumens include catheters forperforming a variety of sensing, material delivery or surgical tasks andstents which can be implanted in blood vessels for the purpose ofpreventing stenosis or restenosis of blood vessels. Capsules containingsensing and imaging instrumentation that may be swallowed by a subjectand which travel passively through the digestive tract have also beendeveloped. Robotic devices intended to move through the lower portion ofthe digestive tract under their own power are also under development.

SUMMARY

The present application describes methods for controlling movement of alumen traveling device through a body tube tree, as well as associatedsystems and devices.

In an embodiment, a system includes non-transitory machine readablemedia, for use in a lumen traveling device control system, including oneor more instructions that cause the lumen traveling device controlsystem to identify at least two possible directions of travel of a lumentraveling device through a body tube tree, the body tube tree includinga plurality of branched, interconnected channels, and the at least twopossible directions of travel corresponding to at least two of thebranched, interconnected channels; one or more instructions that causethe lumen traveling device control system to receive data representing astored parameter value relating to a previous event associated with atleast one of the at least two possible directions of travel; one or moreinstructions that cause the lumen traveling device control system toselect a direction of travel from the at least two directions of travelbased at least in part on the data representing a stored parameter valuerelating to a previous event associated with at least one of the atleast two possible directions of travel; and one or more instructionsthat cause the lumen traveling device control system to direct at leastone of a steering mechanism and a propelling mechanism on the lumentraveling device to cause the lumen traveling device to move through thebody tube tree in the selected direction of travel.

In an embodiment, a method of operating a lumen traveling device with alumen traveling device control system includes identifying at least twopossible directions of travel of a lumen traveling device through a bodytube tree, the body tube tree including a plurality of branched,interconnected channels, and the at least two possible directions oftravel corresponding to at least two of the branched, interconnectedchannels; receiving data representing a stored parameter value relatingto a previous event; selecting a direction of travel from the at leasttwo directions of travel based at least in part on the data representinga stored parameter value relating to a previous event; and directing atleast one of a steering mechanism and a propelling mechanism on thelumen traveling device to cause the lumen traveling device to movethrough the body tube tree in the selected direction of travel.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates an embodiment of a lumen traveling device;

FIG. 2 is a block diagram an embodiment of a lumen traveling device;

FIG. 3 illustrates an embodiment of a propelling mechanism;

FIGS. 4A-4E illustrate an additional embodiment of a propellingmechanism;

FIG. 5 illustrates an embodiment of a lumen traveling device;

FIGS. 6A-6D illustrate several embodiments of active portions of a lumentraveling;

FIG. 7 illustrates an embodiment of a lumen traveling device systemincluding a remote device;

FIG. 8 illustrates an embodiment of control circuitry of a lumen-traveldevice system;

FIG. 9 illustrates an embodiment of logic for controlling a lumentraveling device system;

FIG. 10 illustrates an embodiment of logic for controlling a lumentraveling device;

FIG. 11 illustrates a block diagram of a system;

FIG. 12 illustrates a method of operating a lumen traveling device;

FIG. 13 illustrates embodiments of sensing and storing information;

FIG. 14 illustrates a method of generating a map;

FIG. 15 illustrates embodiments of performing an action with an activeportion of a lumen traveling device;

FIG. 16 illustrates embodiments of performing an action with an activeportion of a lumen traveling device;

FIG. 17 illustrates embodiments of performing an action with an activeportion of a lumen traveling device;

FIG. 18 illustrates embodiments of performing an action with an activeportion of a lumen traveling device;

FIG. 19 illustrates embodiments of performing an action with an activeportion of a lumen traveling device;

FIGS. 20A & 20B illustrate an example of the operation of a lumentraveling device in the lumen of a body tube tree;

FIG. 21 illustrates a block diagram of a system;

FIGS. 22A-22E illustrate a method of operating a lumen traveling-deviceand variants thereof;

FIGS. 23A-23D illustrate an example of the operation of a lumentraveling device in the lumen of a body tube tree;

FIG. 24 illustrates a block diagram of a system;

FIGS. 25A-25E illustrate a method of operating a lumen traveling deviceand variants thereof;

FIGS. 26A-26C illustrate an example of the operation of a lumentraveling device in the lumen of a body tube tree;

FIG. 27 illustrates a block diagram of a system;

FIGS. 28A-28F illustrate a method of operating a lumen traveling deviceand variants thereof;

FIG. 29 illustrates a block diagram of a system;

FIGS. 30A-30D illustrate a method of operating a lumen traveling deviceand variants thereof;

FIG. 31 illustrates a block diagram of a system;

FIGS. 32A-32J illustrate a method of operating a lumen traveling deviceand variants thereof;

FIG. 33 illustrates a block diagram of a system;

FIGS. 34A-34E illustrate a method of operating a lumen traveling deviceand variants thereof;

FIG. 35 illustrates steps for generating a map of a body tube tree;

FIG. 36 is an illustration of a map system;

FIG. 37 is an illustration of a map system;

FIG. 38 illustrates embodiments of planning a path of travel;

FIG. 39 illustrates a block diagram of a system;

FIG. 40 illustrates a method of operating a lumen traveling device;

FIGS. 41A & 41B illustrate placement of a lumen traveling device in abody tube tree;

FIG. 42 illustrates a method of operating a lumen traveling device;

FIG. 43 illustrates a block diagram of a system;

FIG. 44 illustrates an example of the operation of a lumen travelingdevice in the lumen of a body tube tree;

FIG. 45 illustrates a method of operating a lumen traveling device;

FIG. 46 illustrates a block diagram of a system;

FIG. 47 illustrates a method of operating a lumen traveling device;

FIG. 48 illustrates a method of operating a lumen traveling device;

FIG. 49 illustrates a block diagram of a system;

FIG. 50 illustrates a method of operating a lumen traveling device;

FIG. 51 illustrates a block diagram of a system;

FIG. 52 illustrates a method of operating a lumen traveling device;

FIG. 53 illustrates a block diagram of a system;

FIG. 54 illustrates a method of operating a lumen traveling device;

FIG. 55 illustrates a block diagram of a system;

FIG. 56 illustrates a method of operating a lumen traveling device;

FIG. 57 illustrates a block diagram of a system;

FIG. 58 illustrates a method of operating a lumen traveling device;

FIG. 59 illustrates a block diagram of a system;

FIG. 60 illustrates a method of operating a lumen traveling device;

FIG. 61 illustrates a block diagram of a system;

FIG. 62 illustrates a method of operating a lumen traveling device;

FIG. 63 illustrates a block diagram of a system;

FIG. 64 illustrates a method of operating a lumen traveling device;

FIG. 65 illustrates a block diagram of a system;

FIG. 66 illustrates a method of operating a lumen traveling device;

FIG. 67 illustrates a block diagram of a system;

FIG. 68 illustrates a block diagram of a system;

FIG. 69 illustrates a method of operating a lumen traveling device; and

FIG. 70 illustrates a block diagram of a system.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here.

A lumen traveling device is an example of a lumenally active device.Lumenally active devices, and related methods and systems, are describedin U.S. Patent Publication No. 2007/0066929 titled “Lumenally-ActiveDevice,” published Mar. 22, 2007, which is incorporated herein byreference.

An embodiment of a lumen traveling device 10 is illustrated in FIG. 1and includes a structural element 12 configured to travel within atleast a portion of a body lumen 14. The structural element 12 of lumentraveling device 10 includes a fluid-contacting portion 16 configured tocontact fluid within the body lumen, a propelling mechanism 18 capableof producing movement of the structural element 12 through a body lumen14 in which the structural element is deployed, a sensor 20 capable ofsensing a local parameter value in the body lumen, on-board controlcircuitry 22 configured to control the operations of the lumen travelingdevice 10; and an active portion 24 operatively connected to on-boardcontrol circuitry 22 and capable of producing a response upon receipt ofa signal from on-board control circuitry 22. Body lumen 14 is defined bywall portions 26, which are the walls of a blood vessel or other lumen,or a plurality of lumen defining a body tube tree within the body of anorganism. In this example, a body fluid flows through body lumen 14 inthe direction indicated by the arrow. Fluid flows through the centralopening 28 of structural element 12, with the interior surface of thestructural element 12 forming fluid-contacting portion 16. In theembodiment depicted in FIG. 1, sensor 20 and active portion 24 arelocated at a fluid-contacting portion 16. The on-board control circuitry22 further includes one or more of motion control circuitry, mappingcircuitry, and response control circuitry. On-board control circuitry 22serves as a lumen-traveling device control system 30 that is locatedentirely on-board lumen traveling device 10 in this example. In thisexample, the propelling mechanism 18 is one or more rotating wheels thatfrictionally engage wall portions 26 and function to move lumentraveling device 10 through body lumen 14. In other aspects of lumentraveling devices, other structures and methods for engaging the lumenwall and/or propelling the lumen traveling device through the lumen maybe employed.

A lumen traveling device or system is configured for use in (e.g.,configured to fit within and travel within) the lumens of a body tubetree of an organism. Examples of body tube trees of an organism includebut are not limited to the respiratory tract, the cardiovascular system(e.g., blood vessels), a portion of the cerebrospinal fluid (CSF) spaceof the nervous system (e.g., the central canal of the spinal cord, theventricles of the brain, the subarachnoid space, intrathecal space,etc.), the urinary tract, the lymphatic system, a portion of theabdominal cavity, a portion of the thoracic cavity, the digestive tract,the female reproductive tract (e.g., a lumen of a fallopian tube), themale reproductive tract (including various lumens including but notlimited to the epididymis, vas deferens or ductus deferens, efferentduct, ampulla, seminal duct, ejaculatory duct, or urethra), the biliarytract, a nostril or nasal cavity, the oral cavity, the tear ducts, or aglandular system. Other body lumens include those found in the auditoryor visual system, or in interconnections thereof, e.g., the Eustachiantubes. Some of the devices and systems described herein can be used in abody tube tree through which fluid flows, but it is not intended thatsuch devices or systems are limited to use in tubular lumen-containingstructures containing moving fluid; in some applications a lumentraveling device can be used in a body tube tree containing relativelyunmoving or intermittently moving fluid. In a further embodiment, thelumen traveling device can be used in a man-made lumen within the body,including, for example, vascular catheters, spinal fluid shunts,vascular grafts, bowel re-anastomoses, bypass grafts, indwelling stentsof various types (e.g., vascular, gastrointestinal, tracheal,respiratory, ureteral, genitourinary, etc.) and surgically createdfistulas.

The term fluid, as used herein, refers to liquid, gases or othercompositions, mixtures, or materials exhibiting fluid behavior. Thefluid within the lumen of a body tube tree can include a liquid, a gasor gaseous mixtures. As used herein, the term fluid can encompassliquids, gases, or mixtures thereof that also include solid particles ina fluid carrier. Liquids can include mixtures of two or more differentliquids, solutions, slurries, or suspensions. Body fluids can includecomponents such as, for example, cells, cellular fractions orcomponents, collections or aggregations of cells, bacterial, viral orfungal species, ions, molecules, gas bubbles, dissolved gas, suspendedparticles, or a variety of other materials that may be present in thebody fluid. Body fluid components can be materials that are normallypresent in the body fluid, materials that are naturally derived but notnormally present in the body fluid, or foreign materials that haveentered or been introduced to the body fluid (including but not limitedto pathogens, toxins, pollutants, medications, for example). Examples ofliquids present within body lumens include blood, lymph, serum, urine,semen, digestive fluids, tears, saliva, mucous, cerebrospinal fluid,intestinal contents, bile, epithelial exudate, or esophageal contents.Liquids present within body lumens can include synthetic or introducedliquids, such as blood substitutes, or drug, nutrient, or salinesolutions. Fluids can include liquids containing dissolved gases or gasbubbles, or gasses containing fine liquid droplets or solid particles.Gases or gaseous mixtures found within body lumens can include inhaledand exhaled air, e.g., in the nasal or respiratory tract, or intestinalgases.

FIG. 2 is a block diagram depicting components of an embodiment of lumentraveling device 100. Lumen traveling device 100 includes afluid-contacting portion 102 configured to contact fluid within thelumen of the body tube tree and to at least intermittently permit flowof fluid through the lumen; a propelling mechanism 104 capable ofproducing movement of the lumen traveling device through the lumen of abody tube tree in which the lumen traveling device is deployed; a motionarresting portion 106 capable of stopping the movement of the lumentraveling device; motion control circuitry 108 carried at least in partby said lumen traveling device and configured to control propellingmechanism 104 and motion arresting portion 106 to control movement ofthe lumen traveling device through the lumen of a body tube tree; asensor 110 capable of sensing a local parameter value in the lumen of abody tube tree and generating a sense signal indicating detection of thelocal parameter value; response control circuitry 112 operativelyconnected to sensor 110 and configured to generate a response controlsignal upon receipt of the sense signal indicating detection of a localparameter value in the lumen of a body tube tree; mapping circuitry 114operatively connected to motion control circuitry 108 and configured toinform control of movement in the body tube tree based at least in parton a map of the body tube tree; and an active portion 116 operativelyconnected to response control circuitry 112 and capable of producing aresponse upon receipt of the response control signal. Motion controlcircuitry 108, response control circuitry 112, and mapping circuitry 114make up part of on-board control circuitry 107, which can also includeother components not specifically described herein. On-board controlcircuitry 107 in this embodiment also constitutes lumen traveling devicecontrol system 30. Lumen traveling device control system 30 includesnon-transitory machine readable media 111, which stores instructionsand/or data for implementation of/use by on-board control circuitry107/lumen traveling device control system 30. The embodiment of FIG. 2also includes a steering mechanism 118 under control of the motioncontrol circuitry 108 and capable of modifying the direction of movementof the lumen traveling device through the body tube tree. The embodimentof FIG. 2 can include power source 120 configured to provide power to atleast one of propelling mechanism 104, motion arresting portion 106,steering mechanism 118, motion control circuitry 108, mapping circuitry114, sensor 110, response control circuitry 112 and active portion 116.Components of the embodiment of FIG. 2 can be generally as describedelsewhere herein. The lumen traveling device depicted in schematic formin FIG. 2 is a self-contained and self-sufficient device that does notrequire connections to an external controller or power source, and iscapable of untethered use. In some embodiments, methods and systems asdescribed herein can be used in connection with untethered lumentraveling devices. In some embodiments, methods and systems as describedherein can be used in connection with tethered lumen traveling devices(i.e., lumen traveling devices connected to a power source, controller,etc. located outside the body of the subject or, in some cases, at alocation within the body of the subject but remote from the lumentraveling device) via a wire, cable, line, cord or the like.

A lumen traveling device as described for example in connection withFIG. 2 can be configured to fit within a particular lumen of a body tubetree through appropriate selection of device dimensions, materialproperties, and propelling mechanism. Configuration aspects can includesize, shape, rigidity/flexibility, porosity, and biocompatibility, amongothers and may depend on both the materials and methods used toconstruct the lumen traveling device. The dimensions and mechanicalproperties (e.g., rigidity) of the lumen traveling device can beselected for compatibility with the location of use in order to providefor reliable movement and/or positioning of the device and to preventdamage to the lumen of the body tube tree. For example, the dimensionsof a lumen traveling device may be selected to allow the device to fitwithin the smallest lumens expected to be found in the body tube tree ofinterest. Alternatively, the dimensions of a lumen traveling device maybe selected to allow the device to fit into a subset of lumens of a bodytube tree. As an example, the inner diameter of the lumen of thevascular body tube tree can range from about 2 to 2.5 centimeters withinthe aorta to less than 20 micrometers in the capillaries. In anembodiment, the lumen traveling device is capable of altering itsdimensions (e.g. changing in length and diameter) to accommodate lumensof varying diameter. For example, see U.S. Patent Application2005/0177223, which is incorporated herein by reference in its entirety.In a further embodiment, a lumen traveling device of fixed dimension canbe designed for a particular application, or a set of lumen travelingdevices in several sizes can be designed, from which the best size canbe selected for a particular application and/or particular patient.

In an embodiment, the structural element of a lumen traveling device foruse in a lumen of a body tube tree can be a substantially tubularstructure and may include one or multiple lumens in fluid communicationwith the body lumen. Structural elements can have the form of a shortcylinder, an annulus, an elongated cylinder, or a spiral, for exampleand can further include an adjustable diameter. Elongated forms such ascylinders or spirals may be suitable for use in tubular lumen-containingstructures such as, for example, blood vessels. A spiral structure isdisclosed, for example, in Bezrouk et al, Scripta Medica (BRNO) 2005,78:219-226, which is incorporated herein by reference in its entirety.

In an embodiment, the structural element of the lumen traveling devicecan include a self-expanding material, a resilient material, a meshmaterial, or a combination thereof. The form as well as the materialcomposition of the structural element can be configured to contribute tothe expanding or flexing properties of the structural element. Forexample, the basic form of the structural element can includeperforations, mesh, or slots, or a combination thereof that run alongall or part of the length of the structural element and provideflexibility to the structural element. Spiral, mesh, or slottedstructural elements formed from resilient material, for example, can beused to generate elastic, springy or self-expanding/self-contractingstructural elements. A self expanding or self-contracting structuralelement can be used to facilitate positioning of the structural elementwithin a body lumen of an organism. Flexible material having adjustablediameter, taper, and length properties can also be used. Structuralelements that exhibit expansion/contraction properties can include meshstructures formed of various metals or plastics, and some polymericmaterials, for example. Examples of shape change materials are describedin Bellin et al., Proc. Natl. Acad. Sci. USA, 2006, 103:18043-18047; andShahinpoor & Kim Smart Materials and Structures, 2005, 14:197-214, eachof which is incorporated herein by reference.

Lumen traveling devices are not limited to cylindrical structuralelements having a single central opening. In an embodiment, a structuralelement can be configured to contact and move along a portion of a wallof a body lumen, contacting or engaging the lumen wall over a portion ofits cross-section (as opposed to contacting the lumen wall along itsentire cross-section) without obstructing the movement of fluid withinthe body lumen. Such an embodiment can be approximately hemi-sphericalor hemi-elliptoid. In an embodiment, the lumen traveling device can bepill- or capsule-shaped, adapted to move through a central portion of abody lumen. In an embodiment, the lumen traveling device can have anelongated, flexible (e.g. worm- or snake-like) configuration. Otherexamples are described in U.S. Patent Application 2007/0156211, which isincorporated herein by reference.

The lumen-traveling device can be constructed from a variety ofmaterials by a variety of manufacturing methods. Appropriate materialsinclude, but are not limited to, metals, ceramics, polymers, andcomposite materials having suitable biocompatibility, sterilizability,mechanical, and physical properties. Examples of materials and selectioncriteria are described, for example, in The Biomedical EngineeringHandbook, Second Edition, Volume I, J. D. Bronzino, Ed., Copyright 2000,CRC Press LLC, pp. IV-1-43-31, which is incorporated herein byreference. In a further embodiment, the structural element can include abioactive component (such as a drug releasing coating or bioactivematerial attached to or incorporated into the structural element).Techniques for manufacturing the structural element include, but are notlimited to, injection molding, extrusion, die-cutting,rapid-prototyping, self-assembly, etc., and will depend on the choice ofmaterial and device size and configuration. Sensing portions, activeportions, and propelling mechanisms or structures of the lumen travelingdevice as well as associated circuitry can be fabricated on thestructural element using various microfabrication and/or MEMStechniques, or can be constructed separately and subsequently assembledto the structural element, as one or more distinct components. Examplesof microfabrication techniques include, for example, those disclosed inU.S. Patent Applications 2005/0221529; 2005/0121411; 2005/0126916; andNyitrai et al., “Preparing Stents with Masking & Etching Technology,”26^(th) International Spring Seminar on Electronics Technology, IEEE,May 8-11, 2003, pp. 321-324, each of which is incorporated by reference.

The lumen-traveling device of FIG. 2 includes lumen traveling devicecontrol system 30 including on-board control circuitry 107 configured tocontrol the operation of the lumen traveling device. The operations ofthe lumen traveling device include but are not limited to sensing,moving, mapping, transmitting, receiving, computing, responding andacting within the lumen of a body tube tree. The control circuitry caninclude but is not limited to, motion control circuitry, responsecontrol circuitry and mapping circuitry. The control circuitry making uplumen traveling device control system can include at least onemicroprocessor, and/or at least one of hardware, software, and firmware.The control circuitry can be electrical circuitry and/or other types oflogic/circuitry including, but not limited to, fluid circuitry,chemo-mechanical circuitry, and other types of logic/circuitry thatprovide equivalent functionality. The control circuitry can be locatedin or on the structural element of the lumen traveling device, in or ona remote device separate from the structural element of the lumentraveling device, or in part in or on the lumen traveling device and inpart in or on a remote device. Thus, while in the embodiments of FIGS. 1and 2 the lumen traveling device control system 30 includes on-boardcontrol circuitry 22 and on-board control circuitry 107, respectively,in other embodiments, as will be discussed elsewhere here, the lumentraveling device control system can include control circuitry inmultiple locations both on-board and remote from the lumen travelingdevice. Examples of devices and/or systems for communicating withindevices in the body are described in U.S. Pat. No. 5,843,139; 6,409,674;or 7,125,382; U.S. Patent Application 2002/0198604, each of which isincorporated herein by reference.

The control circuitry of the lumen-traveling device can include motioncontrol circuitry. The motion control circuitry can be configured tocontrol one or more motion arresting portions, one or more propellingmechanisms and/or one or more steering mechanisms of the lumen travelingdevice. The motion control circuitry can be operatively connected to oneor more sensors. The one or more sensors are configured to sense one ormore parameter values in the body tube tree. The motion controlcircuitry is configured to control movement of the lumen travelingdevice at least in part in response to receipt of a sense signalindicating detection of a parameter value of interest in the lumen ofthe body tube tree.

The motion control circuitry component of the lumen traveling devicecontrol system can be connected to the mapping circuitry. The mappingcircuitry of the lumen traveling device can be operatively connected toone or more sensor, and configured to use data regarding one or moresensed parameter values associated with the current position of thelumen traveling device to locate the lumen traveling device on a map ofthe body tube tree or to generate or make corrections to a map of thebody tube tree. The mapping circuitry can be operatively connected tothe motion control circuitry and configured to control at least one of apropelling mechanism, a steering mechanism, and/or a motion arrestingportion and to control the movement of the lumen traveling device atleast in part in response to receipt of data regarding the location ofthe lumen traveling device relative to a map of the body tube tree. Inan embodiment, the mapping circuitry is incorporated into the lumentraveling device. In an embodiment, the mapping circuitry isincorporated into a remote device, which receives data regarding one ormore sensed parameter values at the current location of the lumentraveling device, locates the lumen traveling device on a pre-existingmap of the body tube tree, and transmits information to the motioncontrol circuitry on the lumen traveling device to control movement ofthe lumen traveling device in a selected direction of travel.

The lumen traveling device can be propelled through the lumen of a bodytube tree under control of the motion control circuitry using one ormore propelling mechanisms. The propelling mechanism can be selected forthe type and nature of the lumen to be traveled. For example, a lumentraveling device that walks or rolls along one side of a lumen oremploys more than one mode of propulsion, for example, may adapt well tochanges in lumen cross-section. Examples of propelling mechanisms areprovided in U.S. Pat. Nos. 5,337,732; 5,386,741; 5,662,587; and6,709,388; and in Kassim et al., “Locomotion Techniques for RoboticColonoscopy,” Engineering in Medicine and Biology Magazine, IEEE,May/June 2006 pp. 49-56; Xi et al., Nat. Materials, 2005, 4:180-184; andFreitas, “8.2.1.2 Arteriovenous Microcirculation”; “9.4.3.5 LeggedAmbulation”; “9.4.3.6 Tank-Tread Rolling”; “9.4.3.7 AmoeboidLocomotion”; “9.4.3.8 Inchworm Locomotion”; “Nanomedicine Volume I:Basic Capabilities”; 1999; pp. 211-214, pp. 316-318; Landes Bioscience;Georgetown, Tex., USA; each of which is incorporated herein byreference.

The propelling mechanism of the lumen-traveling device can include oneor more cilium-like structures, for example, as described in U.S. PatentApplication 2004/0008853; Mathieu et al., “MRI Systems as a means ofpropulsion for a microdevice in blood vessels,” Engineering in Medicineand Biology Society, 2003, Proceedings of the 25^(th) AnnualInternational Conference of the IEEE, Sep. 17-21, 2003, 4:3419-3422; Lu& Martel, “Preliminary Investigation of Bio-carriers Using MagnetotacticBacteria,” Proceedings of the 28th IEEE EMBS Annual InternationalConference, Aug. 30-Sep. 3, 2006, pp. 3415-3418; and MARTEL, S.,“Towards MRI-controlled ferromagnetic and MC-1 magnetotactic bacterialcarriers for targeted therapies in arteriolocapillary networksstimulated by tumoral angiogenesis,” Proceedings of the 28th IEEE EMBSAnnual International Conference, Aug. 30-Sep. 3, 2006, pp. 3399-3402,each of which is incorporated herein by reference. The propellingmechanism can include rollers or wheel-like structures, as shown in U.S.Pat. No. 7,042,184 and U.S. Patent Application 2006/0119304, each ofwhich is incorporated herein by reference; screw-like structures, asdisclosed in Ikeuchi et al., “Locomotion of Medical Micro Robot withSpiral Ribs Using Mucus,” Micro Machine and Human Science, 1996,Proceedings of the Seventh International Symposium, Oct. 2-4, 1996, pp.217-222, which is incorporated herein by reference; appendages capableof walking motion, as described, for example, in U.S. Pat. No.5,574,347; Xi et al., Nat. Materials, 2005, 4:180-184; Martel, Int. J.Robotics Res. 2005, 24:575-588, and Edwards, Lin, “Spider pill to seekout disease,” PhysOrg.com, 16 Oct. 2009; each of which is incorporatedherein by reference. Appendage-like structures can be configured tointermittently engage the lumen wall and push the structural elementwith respect to the lumen wall with a walking-type motion, or can beconfigured to push against fluid within the lumen in a paddling orswimming motion. In an embodiment, the propelling mechanism can driverotational movement of a lumen-wall-engaging structure with respect tothe structural element, e.g., as in turning of a wheel or a screwelement to propel the structural element through a lumen. Propellingmechanisms can include mechanical or micromechanical structures drivenby at least one motor, micromotor, or molecular motor, or by expansionor change in configuration of a shape change polymer or metal. Amolecular motor can be a biomolecular motor that runs on a biologicalchemical such as ATP, kinesin, RNA polymerase, myosin dynein,adenosinetriphosphate synthetase, rotaxanes, or a viral protein.

FIG. 3 depicts an embodiment of a lumen traveling device adapted totravel through the lumen of a body tube tree with a propelling mechanismthat produces walking-type motion. In this embodiment, lumen travelingdevice 300 includes a structural element 301 sized to travel within alumen of a body tube tree; at least two lumen wall engaging structuresoperable to alternately engage and disengage the lumen wall 314 (in FIG.3, 6 lumen-wall-engaging structures 302, 304, 306, 308, 310, and 312 areshown); and a propelling mechanism capable of producing relativeextension and retraction of the at least two lumen-wall-engagingstructures with respect to each other in combination with alternateengagement and disengagement of the lumen wall 314 to produce movementof the lumen traveling stimulation device with respect to the lumen wall314. Lumen traveling device 300 may also include motion controlcircuitry carried at least in part by the lumen traveling device andconfigured to control the propelling mechanism to control movement ofthe lumen traveling device through the lumen of a body tube tree. The atleast two lumen-wall-engaging structures may include at least twoappendages configured for walking motion. In the embodiment shown inFIG. 3, legs (lumen-wall-engaging structures) 302 and 304 extend andretract with respect to each other, for example, so that as one legswings forward, the other swings back. Larger or smaller numbers oflegs, distributed in various patterns about the structural element, maybe used to propel the lumen traveling device through the body tube tree,and the embodiment depicted in FIG. 3 represents one possible example.Lumen traveling devices that utilize a walking type propulsion mechanismfor engaging surfaces of the gastrointestinal tract are disclosed inQuaglia et al., J. Micromech. Microeng, 2009, 19 105007 (11 pp), whichis incorporated herein by reference.

Leg structures for lumen traveling devices can be formed of variousmaterials and structures, including but not limited to, nanotubes andnanotube bundles, carbon fibers and carbon fiber bundles, silicon,metal, polymers, and other materials as described herein. The legstructures can be moved to produce walking motion by various mechanisms.In an embodiment, one or more legs can be formed from shape-changingmaterial and moved through change in configuration of the leg structureitself. In an embodiment, the legs can have a substantially rigid orfixed configuration that move by a separate actuation mechanism.Shape-changing materials for use in leg structures or actuators can beof various types, including but not limited to, stacked piezoelectricelements, electroactive polymers, heat sensitive polymers, magneticfield responsive polymers, and ferromagnetic materials, as describedelsewhere herein.

FIGS. 4A-4E depict (in cross-section) a further embodiment of propellingmechanism of a lumen traveling device using one or more motion-arrestingportions and lengthening and shortening of the lumen traveling device toinch along the lumen wall. In this embodiment, lumen traveling device400 includes a motion-arresting portion including a firstlumen-wall-engaging structure 402 on first portion 404 of the lumentraveling device, capable of at least intermittently engaging the wall408 of a lumen of a body tube tree in which the lumen traveling device400 is deployed. The lumen traveling device may also include at leastone second lumen-wall-engaging structure 410 on second portion 412 ofthe lumen traveling device, wherein the propelling mechanism produceslengthening and shortening of the distance, between the firstlumen-wall-engaging structure 402 and the second lumen-wall-engagingstructure 410 in coordination with alternate engagement of the firstlumen-wall-engaging structure 402 and the second lumen-wall-engagingstructure 410 with the wall 408 of the lumen of a body tube tree inwhich the lumen traveling device is deployed. In the present example,the lengthening and shortening of the distance between the first andsecond lumen-wall-engaging structures may take place in region 414, butin other embodiments, the distance between the first and secondlumen-wall-engaging structures may change due to change in position ofthe lumen-wall-engaging structures, e.g., in limbs that move relative toeach other to produce walking-type motion. Portions of the lumentraveling device (e.g. end portion 406) may be of fixed length, in orderto provide a stable location for mounting of control circuitry (notshown). The alternate engagement and disengagement of the lumen wall bythe first and second lumen-wall-engaging structures may produceinchworm-type propulsion of the lumen traveling device through the bodylumen. Lumen traveling device 400 includes a propelling mechanismcapable of producing relative extension and retraction of the at leasttwo lumen-wall-engaging structures (402 and 410) with respect to eachother in combination with alternate engagement and disengagement of thebody lumen wall to produce inch-worm-like movement of the lumentraveling stimulation device with respect to the body lumen wall. Theembodiment of the lumen traveling device depicted in FIGS. 4A-4E has atubular structure with a central lumen 418, to permit movement of fluidthrough the lumen traveling device. FIG. 4A depicts a lumen travelingdevice in which lumen-wall-engaging structures 402 and 410 are extendedto engage with the wall 408. In FIG. 4B, second lumen-wall-engagingstructure 410 has been retracted, and region 414 shortened to causemovement of second portion 412 of lumen traveling device 400 in thedirection indicated by the arrow, to attain the configuration shown inFIG. 4C. Second lumen-wall-engaging structure 410 is then extended toengage the wall 408, and first lumen-wall-engaging structure 402 isretracted, to attain the configuration shown in FIG. 4D. Then, asindicated in the arrow in FIG. 4D, region 414 is extend to move firstportion 404 of lumen traveling device 400 in the direction indicated bythe arrow in FIG. 4D. At the end of the movement cycle, lumen travelingdevice 400 has attained the configuration shown in FIG. 4E. Firstlumen-wall-engaging structure 402 may then be extended to engage wall408, as depicted in FIG. 4A. It will be appreciated that by repeatingthe motion cycle illustrated in FIGS. 4A-4E, movement of the lumentraveling device through the lumen may be accomplished.

The lumen-wall-engaging structures 402 of FIG. 4 can be mechanical ormicromechanical structures, expandable materials, inflatable structures,or shape-changing materials or structures. Structures that are specifiedas being expandable and inflatable can also be contractable ordeflatable, and thus capable of reversible change in dimension.Reversible changes of dimension can be used in generating cyclicalmotions for propelling a lumen traveling device. Nevertheless, it iscontemplated that, in some applications, materials and structures thatchange dimension in one direction (only expansion or only contraction)may be used.

In addition to lumen-wall-engaging structures that expand or extend,structures that engage the lumen wall through other mechanisms (forexample, with suction mechanisms, adhesives, claws or hooks) may beused. See, for example, Dario et al., “A Micro Robotic System forColonoscopy,” Robotics and Automation, 1997, Proceeding 1997 IEEEInternational Conference, Apr. 20-25, 1997, 2:1567-1572 and Dongxiang &Guozheng, “An earthworm based miniature robot for intestinalinspection,” Micromachining and Microfabrication Process TechnologyDevices, Proceedings Vol. 4601, Tien & Huang, Ed., pp. 396-400, 2001,each of which is incorporated herein by reference. Lumen travelingdevices that utilize an inchworm-type propulsion mechanism with suctionmechanisms for engaging the surface of the heart are disclosed inPatronik et al., “Improved Traction for a Mobile Robot Traveling on theHeart,” Proceedings of the 28^(th) IEEE EMBS Annual InternationalConference, Aug. 30-Sep. 3, 2006, pp. 339-342, which is incorporatedherein by reference.

In an embodiment of a propelling mechanism, multiple lumen-wall-engagingstructures, operating in sequence to alternately engage and disengagethe lumen wall, can be configured to produce “peristaltic” motion of thelumen traveling device. Examples of devices that produce this type ofmotion are described in U.S. Pat. No. 6,764,441; U.S. Patent Application2006/0004395; Mangan et al., “Development of a Peristaltic Endoscope,”Robotics and Automation, 2002, Proceedings, ICRA '02, IEEE InternationalConference, 1:347-352; and Meier et al., “Development of a compliantdevice for minimally invasive surgery,” Proceedings of the 28^(th) IEEEEMBS Annual International Conference, Aug. 30-Sep. 3, 2006, pp. 331-334,each of which is incorporated herein by reference.

In an embodiment, the propelling mechanism of a lumen traveling devicecan be configured to drive movement of the lumen traveling device alonga wire, catheter, cannula, or tube within the lumen of a body tube tree.

In an embodiment, the lumen traveling device can be propelled throughthe body tube tree by one or more paddles, propellers, flagella, cilia,or the like, which push against fluid contained within the lumen ratherthan engaging the wall of the lumen, e.g. as described in U.S. Pat. No.6,240,312 or in Behkam & Sitti, “Towards hybrid swimming microrobots:Bacteria assisted propulsion of polystyrene beads,” Proceedings of the28^(th) IEEE EMBS Annual International Conference, Aug. 30-Sep. 3, 2006,pp. 2421-2424, each of which is incorporated herein by reference. Otherillustrative examples of propelling mechanisms for lumen travelingdevices are described in U.S. Patent Application 2007/0156211, which isincorporated herein by reference. In many cases, the direction ofmovement produced by the various propelling mechanisms described hereinmay be reversed by simply reversing the operation of the propellingmechanisms.

Movement of the lumen traveling device in a given direction of travelcan be reduced or stopped by one or more motion-arresting portions undercontrol of the motion control circuitry. A motion-arresting portion cantake various forms, including, for example, an anchor capable ofattaching at least temporarily to a wall of the lumen, at least one hookor claw, at least one adhesive material or glue, a brake to oppose theaction of the propelling mechanism, or a shutoff for the propellingmechanism. The motion-arresting portion can further include a reversalmechanism for the propelling mechanism, in that to arrest motion it maybe necessary to provide sufficient propulsion in the reverse directionto oppose a flow of fluid through the body lumen. The motion-arrestingportion can be a part of, or associated with, the propelling mechanism(e.g. a shutoff or reversal mechanism for the propelling mechanism) orit can be a separate mechanism (adhesive, hook- or claw-like structure,anchor, etc.).

The lumen traveling device can be configured to include a steeringmechanism under control of the motion control circuitry. The steeringmechanism can be any of various structures, depending on the type ofpropelling mechanism used. For example, if the propelling mechanism is apaddle or propeller that causes the lumen traveling device to move inthe fluid in the lumen, the steering mechanism can be a rudder. If thepropelling mechanism includes multiple wheels or limb-like structures,the wheels or limb-like structures can be activated differentially ondifferent sides of the lumen traveling device to steer it in onedirection or another. In an embodiment in which the lumen travelingdevice contacts the lumen walls on all sides of the lumen travelingdevice, the steering mechanism may be used only in the cases that thelumen traveling device encounters a branch point in the lumen, and oncethe front portion of the lumen traveling device (defined by thedirection of travel) is steered to cause the device to enter a selectedbranch, the back portion of the device will follow without the need foradditional steering.

As illustrated in FIG. 2, the control circuitry, including the motioncontrol circuitry, the mapping circuitry, and the response controlcircuitry, is operatively connected to one or more sensors. The one ormore sensors are configured to sense one or more local parameter valuesin the lumen of a body tube tree. Sensed local parameter values can beused in mapping and motion control functions, and to control use of thelumen traveling device to perform actions or deliver treatments with theactive portion. The lumen traveling device can include various types ofsensing or information gathering devices or structures, including butnot limited to, one or more pressure sensors, temperature sensors, flowsensors, viscosity sensors, shear sensors (e.g., for measuring theeffective shear modulus of the fluid at a frequency or strain-rate), pHsensors, gas sensors, chemical sensors for determining the presenceand/or concentration of a chemical compound or species, optical sensorsand/or image sensors (e.g., charged couple device (CCD) array), acousticsensors, biosensors, electrical sensors, magnetic sensors, clocks ortimers. Examples of sensor types are provided in U.S. Pat. Nos.5,522,394; 5,873,835; 6,053,873; 6,409,674; 6,111,520; 6,278,379;6,475,639; 6,802,811; 6,855,115, and U.S. Patent Applications2005/0277839 and 2005/0149170, each of which is incorporated herein byreference. It will be appreciated that an “image sensor” includes anytype of sensor that can detect or construct a two- or higher-dimensionalrepresentation of values of a parameter of interest, including but notlimited to optical images, thermal images, acoustic images, and soforth. In some embodiments, an active portion of a lumen travelingdevice can include a sensing or information gathering device orstructure, and the action performed by the active portion of the lumentraveling device can include detecting or sensing information; forexample, an action performed by an active portion of a lumen travelingdevice can include detecting an image.

In an embodiment, the one or more sensors of the lumen traveling deviceare optical sensors. An optical sensor can be configured to measure theoptical absorption, optical emission, fluorescence, or phosphorescenceof at least a portion of the body tube tree, including for example, thefluid in the lumen, the surface of the lumen wall, the interior of thelumen wall, or a combination thereof. Such optical properties may beinherent optical properties of all or a portion of the fluid or lumenwall, or may be optical properties of materials added or introduced tothe fluid or lumen wall, such as markers, labels, or tags for materialsor structures of interest. Optical sensing of materials in blood, forexample, is described in Manley et al., “Blood characterization usingUVNIS spectroscopy,” Proc. SPIE Advances in Fluorescence SensingTechnology II, Joseph R. Lakowicz, Ed., Vol. 2388, p. 462-470, 1995 andU.S. Pat. Nos. 5,589,932 and 7,027,134, each of which is incorporatedherein by reference.

In an embodiment, the one or more sensors of the lumen traveling deviceare biosensors configured to sense materials including, but not limitedto, a biological marker, an antibody, an antigen, a peptide, apolypeptide, a protein, a complex, a nucleic acid, oligonucleotide, apolynucleotide, a cell (and, in some cases, a cell of a particular type,e.g. by methods used in flow cytometry), a cell fragment, a cellularcomponent, a platelet, an organelle, a gamete, a pathogen, a signalingmaterial (including bacterial and viral signaling materials, forexample, as well as endogenous cell-signaling materials), a lipid, alipoprotein, an alcohol, an acid, an ion, an immunomodulator, a sterol,a steroid, a carbohydrate, a sugar, a polysaccharide, a glycoprotein, ametal, an electrolyte, a metabolite, an organic compound, anorganophosphate, a drug, a therapeutic, a gas, a pollutant, or a tag. Abiosensor can include one or more binding molecule, examples of whichinclude antibodies, aptamers, receptors, ligands, synthetic antibodies,etc. (see, e.g., Mok & Li, Sensors, 2008, 8:7050-7084, which isincorporated herein by reference).

A sensor can include a single sensor or an array of sensors, and is notlimited to a particular number or type of sensors. The one or moresensors can be very small, including a sensor or array that is achemical sensor (Snow, Science, 2005, 307:1942-1945), a gas sensor(Hagleitner et al., Nature, 2001, 414:293-296), an electronic nose, anuclear magnetic resonance imager (Yusa et al., Nature, 2005,343:1001-1005). Each of the foregoing references is incorporated hereinby reference. Further examples of sensors are provided in The BiomedicalEngineering Handbook, Second Edition, Volume I, J. D. Bronzino, Ed.,Copyright 2000, CRC Press LLC, pp. V-1-51-9; Morrison et al., “ClinicalApplications of Micro- and Nanoscale Biosensors,” in BiomedicalNanostructures, Edited by K. E. Gonsalves, C. L. Laurencin, C. R.Halberstadt, L. S, Nair. 2008, John Wiley & Sons, Inc.; and U.S. Pat.No. 6,802,811, each of which is incorporated herein by reference.

The one or more sensors are configured to send signals to the controlcircuitry of the lumen traveling device regarding local parameter valuesin the environment of the body tube tree through which the lumentraveling device is traveling. The control circuitry of the lumentraveling device further includes, but is not limited to, motion controlcircuitry, mapping circuitry and response control circuitry. In responseto a signal from a sensor, the motion control circuitry can send one ormore signals instructing the lumen traveling device to move or arrest.In response to a signal from a sensor, the mapping circuitry can sendone or more signals instructing the lumen traveling device to move or toperform an action based on a pre-existing or evolving map of the bodytube tree. In response to a signal from a sensor, the response controlcircuitry can send one or more signals instructing the lumen travelingdevice to perform an action using one or more of an active portion. Inan embodiment, the control circuitry responsive to one or more sensorsis located in or on the lumen traveling device. In a further embodiment,at least a portion of the control circuitry is located in or on a remotedevice in communication with the lumen traveling device.

The lumen traveling device can include one or more active portions undercontrol of the response control circuitry (and, more generally, thelumen traveling device control system) and configured to perform anaction. An active portion of the lumen traveling device is configured toperform an action including but not limited to releasing a material,releasing a device or structure, releasing an energy, collecting asample, collecting a device or structure, attaching a structure to awall of the body tube tree, delivering a material or structure to areceiving portion of a man-made device, receiving a material orstructure from a delivery portion of a man-made device, receiving asignal from a remote source, receiving power from a remote source,transmitting a signal to a remote location, performing a surgical stepor procedure, removing tissue from at least a portion of the body tubetree (e.g., by scraping, shaving, excising, resecting, aspirating,excising by core or punch, biopsying, etc.), removing components of atleast a portion of a fluid from a body tube tree, exposing a catalyst,generating a localized electric field, generating a localized magneticfield, producing heat, causing cooling, emitting electromagneticradiation, emitting acoustic energy, applying pressure to at least aportion of the body tube tree, modulating the flow of a fluid through atleast a portion of the body tube tree, sensing a local parameter value(which may be the same or different than a previously sensed parametervalue), stopping performance of an action if the local parameter valueis within a specified range, and initiating performance of an action ifthe local parameter value is within a specified range. A number ofillustrative examples of active portions of a lumen traveling device forperforming an action are described in U.S. Patent Application2007/0156211, which is incorporated herein by reference. As used herein,“exposing a catalyst” refers to any process by which a catalyst is madeavailable or accessible to a reactant or reactants participating in areaction catalyzed by the catalyst. For example, a catalyst may beexposed by being released from the active portion of the lumen travelingdevice into the body tube tree, or it may be exposed while remaining onor associated with the lumen traveling device. A catalyst may be exposedthrough the removal of a material or structure covering the catalyst, orby the creation or expansion of opening or apertures that permit accessto the catalyst through a material or structure that covers or otherwiselimits access to the catalyst.

As used herein, a “remote source” (e.g., from which power or a signalcan be received, as discussed above) can be a remote device that forms apart of a lumen traveling device system, or it can be a remote sourcethat is not a part of a lumen traveling device system. A remote sourcecan be a power source, a signal source, or both. Examples of remotesources (particularly sources of position indicator signals) aredescribed herein below.

In an embodiment, the active portion of the lumen traveling deviceperforms an action that includes releasing a material. Examples ofmaterial released by the lumen traveling device include but are notlimited to at least one of an adhesive, a filler, a polymer, a hydrogel,an antibiotic, an antibody, an antiviral, a pharmaceutical compound, anutrient, a hormone, a growth factor, a catalyst, a drug, a therapeuticcompound, a chemical, a biomaterial, a biological marker, label, or tag,an enzyme, a protein, a nucleic acid, an oligonucleotide, apolynucleotide, a polypeptide, a genetic material, a cell, a fraction ofa cell, a cell fragment, a complex, a vaccine, a vitamin, aneurotransmitter, a neurotropic agent, a neuroactive material, acytokine, a chemokine, a hormone, a signaling material, a pro-apoptoticagent, an anti-apoptotic agent, an immunological mediator, ananti-inflammatory agent, a salt, an ion, an electrolyte, an antioxidant,an imaging agent, a labeling agent, a diagnostic compound, ananomaterial, an inhibitor, a lipid, an alcohol, a sterol, a steroid, acarbohydrate, a sugar, a gas, or a blocker.

An active portion of a lumen traveling device can include a materialrelease structure operatively coupled to the response control circuitryand configured to release a material in response to receipt of aresponse control signal. FIG. 5 depicts a lumen traveling device 500including a structural element 502, sensor 504, on-board controlcircuitry 505 including response control circuitry 506, and materialrelease structure 508 including release mechanism 510. On-board controlcircuitry 505 can constitute the entirety of the lumen traveling devicecontrol system, or the lumen traveling device control system can includeadditional control circuitry located remotely (not shown in FIG. 5), asdiscussed elsewhere herein. Structural element 502 includes externalsurface 512, configured to fit within a body lumen, and internal surface514 defining central opening 516, through which a fluid may flow. Uponsensing of a condition of interest in the fluid by sensor 504, responsecontrol circuitry 506 sends a response control signal to activaterelease mechanism 510, resulting in release of material from materialrelease structure 508. Release mechanism 510 can include a variety ofdifferent types of release mechanisms, including, for example, acontrollable valve. Various types of valves and microvalves are known tothose of skill in the art, and can be used to regulate the release ofmaterial from material release structure 508 in response to a responseinitiation signal from response control circuitry 506. Examples ofcontrollable valves or microvalves for microelectromechanical systems(MEMS) are provided in Luckevich, Valve-World, May 2007, 79-82, 2007,which is incorporated herein by reference. Response control circuitry506 may activate release mechanism 510 by supplying a response controlsignal, which may be an electrical signal, for example. Other types ofresponse control signals can be used, including magnetic signals,optical signals, acoustic signals, other types of signals, orcombinations thereof. In an embodiment, response control circuitry 506can cause release of material from material release structure 508 inresponse to passage of a certain amount of time, as monitored, forexample, by a timekeeping device. In an embodiment, material releasestructure 508 can include a pressurized reservoir of material. In anembodiment, the material (or materials) to be released is generatedwithin material release structure 508.

The material release structure of the lumen traveling device can includedeformable, degradable, or rupturable barriers formed from a variety ofmaterials, including, but not limited to, metals, polymers, crystallinematerials, glasses, ceramics, semiconductors, etc. Release of materialsthrough rupture or degradation of a barrier is also described in U.S.Pat. No. 6,773,429, and U.S. Patent Application 2004/0260391, each ofwhich is incorporated herein by reference. Semipermeable barriers havingvariable permeability are described, for example, in U.S. Pat. No.6,669,683, which is incorporated herein by reference. In an embodiment,barriers can be formed and operated reversibly through multiple releasecycles. In an embodiment, a rupturable barrier can be used for asingle-release functionality. Additional illustrative examples of lumentraveling device material release structures are provided in U.S. PatentApplication 2007/0156211, which is incorporated herein by reference.

The lumen traveling device can further include a material for releasethat is dispersed in a carrier material. The material can be releasedfrom the carrier material upon activation of a release mechanism.Material can be released into a central opening of the lumen travelingdevice and/or into the area around the lumen traveling device. In anembodiment, the material(s) may diffuse away from the release structurealong a concentration gradient. The carrier material can be, forexample, a polymeric material such as a hydrogel into which the releasedmaterial is dispersed or dissolved. Carrier materials can includeparticles or particle-like structures, e.g. particles, microparticles,nanoparticles, microspheres, nanospheres, liposomes, micelles, proteincages, dendrimers, etc. The release mechanism can be a heating element,for example a resistive element connected directly to response controlcircuitry, or an electrically or magnetically responsive material thatcan be moved, vibrated or heated, by an externally appliedelectromagnetic field, which in turn causes release of material from thecarrier material. See, for example, U.S. Pat. Nos. 5,019,372 and5,830,207, each of which is incorporated herein by reference. An exampleof a magnetically responsive polymer is described, for example, in Netoet al., Brazilian Journal of Physics, 2005, 35:184-189, which isincorporated herein by reference. Other exemplary materials andstructures are described in Pan et al., J. Micromech. Microeng., 2005,15:1021-1026 or in U.S. Pat. No. 6,607,553, each of which isincorporated herein by reference.

In an embodiment, the permeability of the lumen wall to the releasedmaterial can be increased by the use of retractable spines thatpenetrate the lumen wall, as described in U.S. Pat. No. 6,991,617, byhollow microneedles capable of penetrating the lumen wall, as describedin U.S. Pat. No. 6,743,211, by a chemical permeability enhancer asdescribed in U.S. Pat. No. 6,673,363, which may be released from thelumen traveling delivery device along with the material or from aseparate reservoir or other source, or by an electrical permeabilityenhancer, such as a voltage source for producing electroporation, as inU.S. Pat. No. 6,512,950 or 6,022,316, all of which patents areincorporated herein by reference.

In an embodiment, the active portion of the lumen traveling device caninclude a heating element 600 as depicted in FIG. 6A, operativelycoupled to the response control circuitry 601 and configured to produceheating in response to receipt of the response control signal. Theheating element can be a resistive element that produces heat whencurrent is passed through it, or it can be a magnetically activematerial that produces heat upon exposure to an electromagnetic field.Examples of magnetically active materials include permanentlymagnetizable materials, ferromagnetic materials such as iron, nickel,cobalt, and alloys thereof, ferrimagnetic materials such as magnetite,ferrous materials, ferric materials, diamagnetic materials such asquartz, paramagnetic materials such as silicate or sulfide, andantiferromagnetic materials such as canted antiferromagnetic materialswhich behave similarly to ferromagnetic materials; examples ofelectrically active materials include ferroelectrics, piezoelectrics anddielectrics. Heat can also be generated through an exothermic chemicalreaction. U.S. Patent Applications 2002/0147480 and 2005/0149170,provide examples of heating and/or cooling mechanisms and structures,and are incorporated herein by reference. The heating element can beused to at least partially ablate and/or cauterize a target of interestwithin the lumen of a body tube tree.

In an embodiment, the active portion of the lumen traveling device caninclude a cooling element 602 as depicted in FIG. 6B, operativelycoupled to the response control circuitry 603 and configured to causecooling in response to receipt of the response control signal. Coolingcan be caused by a number of mechanisms and/or structures. For example,cooling can be caused by an endothermic reaction (such as the mixing ofammonium nitrate and water) initiated by opening of a valve or actuationof a container in response to a control signal, which in turn removesenergy from its surrounding. Other cooling elements that can be used forcausing cooling include, but are not limited to, thermoelectric (PeltierEffect) and liquid-gas-vaporization (Joule-Thomson) devices.

In an embodiment, the active portion of the lumen traveling device caninclude an electromagnetic radiation source 604 as depicted in FIG. 6C,operatively coupled to the response control circuitry 605 and configuredto emit electromagnetic radiation in response to receipt of the responsecontrol signal. Electromagnetic radiation sources can include lightsources (e.g., light emitting diodes or laser diodes), or sources ofother frequencies of electromagnetic energy or radiation including butnot limited to radio waves, microwaves, ultraviolet rays, infra-redrays, optical rays, terahertz beams, and the like.

In an embodiment, the active portion of the lumen traveling device caninclude an acoustic energy source 606 (e.g. a piezoelectric element) asdepicted in FIG. 6D, operatively coupled to the response controlcircuitry 607 and configured to emit acoustic energy in response toreceipt of the response control signal. An acoustic energy source cangenerate pressure pulses of various frequencies, including auditoryfrequencies, subsonic frequencies, and ultrasonic frequencies. Amicroscale acoustic transducer may be constructed, for example, in U.S.Pat. No. 5,569,968, which is incorporated herein by reference.

In an embodiment, the active portion of the lumen traveling device caninclude an electric field source, operatively connected to the responsecontrol circuitry and configured to apply an electric field to the fluidand/or lumen wall or surrounding tissue in response to receipt of theresponse control signal. The electric field source may be a capacitor orother charge storing device, to generate a static electric field, or itmay be current source capable of generating a dynamic electric field.

In an embodiment, the active portion of the lumen traveling device caninclude a magnetic field source operatively connected to the responsecontrol circuitry and configured to apply a magnetic field to the fluidand/or lumen wall or surrounding tissue in response to receipt of theresponse control signal. The magnetic field can be generated by runninga current through a coil or other structure. In an embodiment, one ormore fixed magnets are included in the magnetic field source.

In an embodiment, the active portion of the lumen traveling device caninclude a positioning element operatively coupled to the responsecontrol circuitry and configured to secure the lumen traveling deviceinto position within the body lumen in response to receipt of theresponse control signal. Examples of positioning elements include butare not limited to claws, hooks, clips, tensioning elements, expandingelements, and adhesives. Certain positioning elements may be suited toretaining the lumen traveling device in a location for extended periods(e.g., an adhesive), while other positioning elements may be more suitedto retaining the lumen traveling device in a location only briefly(e.g., a retractable hook). Other illustrative examples of positioningelements of a lumen traveling device are described in U.S. PatentApplication 2007/0156211, which is incorporated herein by reference.

In an embodiment, the active portion of the lumen traveling device caninclude a separator operatively connected to the response controlcircuitry and configured to selectively remove specific components fromthe fluid or wall of the lumen in response to detection of the localcondition of interest. Separators can include but are not limited to,one or more molecular sieve or mechanical filter (including, forexample, screen, mesh, fiber, etc) having openings sized to allowpassage of particles or structures of a particular size or size range,or one or more chemical or biochemical separators configured to separatematerials based on binding affinity, charge, surface energy, etc. Forexample, U.S. Patent Application 2005/0126916 provides an example of amicrofabricated mesh while U.S. Patent Application 2008/0241847 providesan example of a probe for in vivo collection of circulating molecules.Each of the foregoing references is incorporated herein by reference. Aseparator can be configured to remove undesirable components from thefluid. Alternatively, a separator can be configured to remove componentsfor the purpose of collecting a sample for analysis.

In an embodiment the active portion of the lumen traveling device caninclude a sample collector for collecting fluid or solid samples. Theliquid and/or solid sample can be immediately analyzed or placed in asample collection structure for future analysis. Examples of samplecollection structures and mechanisms are provided in U.S. Pat. Nos.6,436,120 and 6,712,835, and Hanna et al., IEEE Trans. Nanobioscience,2003, 2:6-13, each of which is incorporated herein by reference. Theactive portion can include a tool for collecting a solid sample (e.g.,arterial plaque, tumor), for example, for biopsy and/or for removal ofdamaged, diseased, or otherwise unwanted tissue. The active portion caninclude one or more tools, especially surgical tools, e.g., for cutting,scraping, suturing, cauterizing, or injecting or aspirating. An exampleof a scraping tool is presented in JP 2005-74229, which is incorporatedherein by reference. Other examples of biopsy tools associated withintralumenal devices are described in US Patent Application 2009/0069821and U.S. Pat. No. 6,679,893, each of which is incorporated herein byreference.

In an embodiment, the active portion of the lumen traveling device caninclude a fluid capture portion operatively coupled to the responsecontrol circuitry and configured to capture a material of interest. Afluid capture portion can be a reservoir, for example, into which fluidis drawn by capillary action or by a negative pressure generated by apump, for example. Captured fluid can be treated and released, or simplystored. In some applications, captured fluid may be subjected toanalysis as described in U.S. Patent Application 2009/0082652, which isincorporated herein by reference. Fluid and/or constituents thereof,including cells or other biologics, can be passively collected within amatrix material associated with the lumen traveling device. The matrixmaterial can include an absorbent such as cotton, cellulose, natural orartificial sponge, a gel (e.g., a natural gel such as agarose, a naturaland/or synthetic polymer gel, or a hydrogel), a colloid, a gum base suchas acacia gum, or micro particles. The sample collection portion caninclude a lipid monolayer, lipid bilayer, liposome, dendrimer, ligandaffinity resin with conjugated peptide or antibody, ionophore, hydrosol,sol-gel, xerogel, aerogel, smart gel, hydrocarbon gel, or ferrogel.Alternatively, the sample collector can include a synthetic or naturaladsorbent material such as a proteoglycan or charged polymer likepolylysine, that promotes the adhesion of one or more fluid constituent,e.g. a cell or protein. Other materials include semi-specific ornon-specific absorbers, such as silica (SiO₂) or alumina (Al₂O₃) gel orion exchange resin, possibly as part of the matrix material. Furtherexamples of materials for sample collection are disclosed in U.S. Pat.Nos. 6,861,001 and 6,475,639, each of which is incorporated herein byreference. Alternatively or in addition, the sample collector caninclude one or more recognition elements of a type able to recognizeand/or specifically bind a constituent of the fluid. Examples ofrecognition elements include but are not limited to, staphylococcusprotein A complex, which generally binds immunoglobulins; a bindingpeptide or protein like an immunoglobulin; a ligand; a receptor; anucleic acid; a carbohydrate; a lipid; a conjugate; or a syntheticmolecule like an artificial antibody or other mimetic. U.S. Pat. Nos.6,255,361; 5,804,563; 6,797,522; and 5,831,012 and U.S. PatentApplication 2004/0018508, each of which is incorporated herein byreference provide examples of such mimetics.

In an embodiment, the active portion of the lumen traveling device canbe configured to suture a portion of the lumen of a body tube tree.Various examples of suturing tools are disclosed and described in U.S.Pat. Nos. 7,131,979 and 5,964,773, each of which is incorporated hereinby reference. Tools may be micro-scale tools formed by MEMSmanufacturing techniques, for example, as described in U.S. Pat. No.5,728,089, which is incorporated herein by reference. It will beappreciated that various other active portions disclosed herein may alsohave surgical utility: for example, active portions for performingsample collection, material release, heating, cooling, etc. may all havesurgical applications.

In an embodiment, the active portion of a lumen traveling device caninclude an attachment structure operatively coupled to the responsecontrol circuitry and configured to attach to a structure (particularlya man-made structure) present in the body lumen in response to receiptof the response control signal. The attachment structure can includevarious mechanical mechanisms, e.g., a grasper or hook, or be based onmagnetic attraction, electrostatic forces, chemical bonding, surfaceinteractions, etc. Microscale structures for gripping or grasping aredescribed in U.S. Pat. No. 6,398,280, and Leong et al., Proc. Natl.Acad. Sci. USA, 2009, 106:703-708, each of which is incorporated hereinby reference.

The active portion as well as other operational components of the lumentraveling device is operatively coupled to the control circuitry. In anembodiment, as depicted in FIG. 7, at least a portion of the controlcircuitry that controls the operation of lumen traveling device 100 islocated in remote device 122, outside the body of the subject, or at alocation within the body of the subject at a distance from the lumentraveling device. In the embodiment depicted in FIG. 7, lumen travelingdevice system 700 includes lumen traveling device 100 and remote device122. In general, a lumen traveling device system includes at least onelumen traveling device and at least one remote device, and in someembodiments can include multiple lumen traveling devices and/or multipleremote devices. Lumen traveling device control system 30 is thusdistributed between lumen traveling device 100 and remote device 122.

In the embodiment of FIG. 7, lumen traveling device 100 includes afluid-contacting portion 102 configured to contact fluid within thelumen of the body tube tree and to at least intermittently permit flowof fluid through the lumen; a propelling mechanism 104 capable ofproducing movement of the lumen traveling device through the lumen of abody tube tree in which the lumen traveling device is deployed; a motionarresting portion 106 capable of stopping the movement of the lumentraveling device; motion control circuitry 108 carried at least in partby said lumen traveling device and configured to control propellingmechanism 104 and motion arresting portion 106 to control movement ofthe lumen traveling device through the lumen of a body tube tree; asensor 110 capable of sensing a local parameter value in the lumen of abody tube tree and generating a sense signal indicating detection of thelocal parameter value; response control circuitry 112 operativelyconnected to sensor 110 and configured to generate a response controlsignal upon receipt of the sense signal indicating detection of a localparameter value in the lumen of a body tube tree; mapping circuitry 114operatively connected to motion control circuitry 108 and configured toinform control of movement in the body tube tree based at least in parton a map of the body tube tree; and an active portion 116 operativelyconnected to response control circuitry 112 and capable of producing aresponse upon receipt of the response control signal. Motion controlcircuitry 108, response control circuitry 112, and mapping circuitry 114make up part of on-board control circuitry 107, which may also includeother components not specifically described herein. The embodiment ofFIG. 7 also includes a steering mechanism 118 capable of modifying thedirection of movement of the lumen traveling device; wherein the motioncontrol circuitry 108 can be configured to control the steeringmechanism 118 to control movement of the lumen traveling device throughthe body tube tree. The embodiment of FIG. 7 includes power source 120configured to provide power to at least one of propelling mechanism 104,motion arresting portion 106, steering mechanism 118, motion controlcircuitry 108, mapping circuitry 114, sensor 110, response controlcircuitry 112 and active portion 116. At least a portion of the controlcircuitry for lumen traveling device 100 can be remote control circuitry124 located remote from lumen traveling device 100 in remote device 122.Remote control circuitry 124 can include a remote portion of the motioncontrol circuitry, remote motion control circuitry 128, a remote portionof the response control circuitry, remote response control circuitry130, and a remote portion of the mapping circuitry, remote mappingcircuitry 132. Lumen traveling device 100 can includereceiver/transmitter 134 with data reception and/or transmissioncircuitry configured to receive a wireless control signal from remotemotion control circuitry 128, transmitted from remotereceiver/transmitter 136. Receiver/transmitter 134 and remotereceiver/transmitter 136 are parts of on-board control circuitry 107 andremote control circuitry 124, respectively. As shown in FIG. 7, lumentraveling device control system 30 includes remote control circuitry 124and on-board control circuitry 107. Lumen traveling device controlsystem 30 may include non-transitory machine readable media 111 a, whichstores instructions and/or data for implementation of/use by on-boardcontrol circuitry 107 and non-transitory machine readable media 111 b,which stores instructions and/or data for implementation of/use byremote control circuitry 124. Data, e.g., sensed parameter values,device location, etc., can be transmitted from lumen traveling device100 to remote device 122 via receiver/transmitter 134. Remote device 122includes a remote power source 138. In some embodiments, power can betransmitted to lumen traveling device 100 from remote device 122 viapower transmitter 140 and power received 142. An example of a telemetrycommunication system using radiofrequency (RF) is described in Sun etal., J. Med. Eng. Technol., 2003, 27:160-163, which is incorporatedherein by reference.

In an embodiment of lumen traveling devices or systems, a lumentraveling device can be a self-contained device that includes allfunctionalities necessary for operation of the lumen traveling device,as illustrated in FIG. 2. In another embodiment, as illustrated in FIG.7, a lumen traveling device system can include a lumen traveling device100 configured to for placement in a body lumen, and at least one remotedevice 122 configured to perform at least some of the functionalities ofthe lumen traveling device system. The lumen traveling device controlsystem 30 is located in part in lumen traveling device 100 and in partin one or more remote devices 122; e.g., lumen traveling device controlsystem 30 includes on-board control circuitry 107 and remote controlcircuitry 124. In an embodiment, all functionalities essential for theoperation of the lumen traveling device are located on the lumentraveling device in on-board control circuitry 107, with a subset ofauxiliary functions located in the remote device in remote controlcircuitry 124. For example, the remote device 122, including remotecontrol circuitry 124, can provide monitoring of the operation of thelumen traveling device, data collection or analysis and/or map building.Remote device 122 can be located within the body of the subject at adistance from the lumen traveling device, or outside the body of thesubject. The remote device 122 can be located near the subject (e.g.,carried or worn on the subject's body or placed on a table near thesubject) or distant from the subject (e.g. in a different room orbuilding, or in a different city, state or country). In an embodiment,the remote device can include a computing device, and can be a cellphone, mobile device, remote controller, a personal digital assistant(PDA), or other handheld device. In an embodiment, the remote device canbe a computer system such as, for example, a laptop computer, computerpad, or a computer work station.

Lumen traveling device system 700 can include one or more timingdevices, for example one or both of local timing device 827 a on lumentraveling device 100 and remote timing device 827 b on remote device122. Local timing device 827 a can form a part of on-board controlcircuitry 107, and similarly, remote timing device 827 b can form a partof remote control circuitry 124.

Lumen traveling device 100 can include a transmitter and receiver(receiver/transmitter 134) operatively coupled to the control circuitryand configured to communicate with one or more remote devices 122. Dataand/or power signals can be transmitted between lumen traveling device100 and one or more remote devices 122 using electromagnetic or acousticsignals, or can be carried over electrical or optical links. It will beappreciated that by using a wireless link between the lumen travelingdevice 100 and remote device 122 lumen traveling device 100 can functionas an untethered device that can move freely within the body withoutconnecting cables, wires, lines, catheters, etc. Various types and/orcombinations of types of communications methods and devices may be used,as are known to those of skill in the art. Transmission of informationbetween lumen traveling device 100 and one or more remote devices 122can be via multiple communication channels, in series or in parallel. Inan embodiment, the remote device can be placed in a location where thereis more space available than within the lumen of the body tube tree, orthat is more readily accessible than the lumen of the body tube tree andcan include a portion of the electrical circuitry portion of the lumentraveling device control system (e.g., hardware, firmware, software, orany combination thereof).

Communication of information between lumen traveling device 100 and atleast one remote device 122 (e.g., via receiver/transmitter 134 andremote receiver/transmitter 136) can include communicating an image,communicating a sensed parameter value, communicating a measuredparameter value, communicating a derived parameter value, communicatingdevice status information, or communicating an action performed. Theinformation transmitted by lumen traveling device 100 to a remote device122 can be used to inform a medical caregiver about a condition of thesubject so that suitable treatment may be provided by the caregiver. Insome embodiments, the information transmitted by the lumen travelingdevice 100 to the remote device 122 can contain information usable by alumen traveling device control system to control operation of the lumentraveling device 100. The information transmitted by the lumen travelingdevice 100 to a remote device 122 can also include information regardingthe movement and location of the lumen traveling device 100 to aid indevelopment of a map of the body tube tree by the remote device, e.g. byremote mapping circuitry 132.

The lumen traveling device 100 can further include a receiver coupled tothe control circuitry and configured to receive a communication from oneor more remote devices 122. Information communicated from the remotedevice 122 to the lumen traveling device 100 can include, but is notlimited to, operating instructions, a map of a body tube tree, and/orimage data or other parameter data collected by at least one remotedevice 122. In an embodiment, information can be transmitted to thelumen traveling device 100 by the remote device 122 in response tocommunications received from the lumen traveling device 100. In anembodiment, a medical caregiver can control communications to the lumentraveling device 100, sending specific instructions and information tothe lumen traveling device 100 through the remote device. Implantablemedical devices with wireless communication capabilities have beendescribed (see, e.g., U.S. Pat. Nos. 6,263,245 and 7,486,967; U.S. Pat.Application 2009/0182388, each of which is incorporated herein byreference). Instructions, data, or other signals transmitted between aremote source (e.g., remote device 122) and lumen traveling device 100can be encrypted. The lumen traveling device system 700 can include,lumen traveling device 100 including for example, but not limited to,one or more cryptographic logic component 115. Similarly, Remote device122 can include remote cryptographic logic component 117. In anembodiment, at least one of the one or more cryptographic logiccomponents 115 and 117 is configured to implement at least onecryptographic process, or cryptographic logic, or combinations thereof.Examples of a cryptographic process include, but are not limited to oneor more process associated with cryptographic protocols, decryptionprotocols, encryption protocols, regulatory compliance protocols (e.g.,FDA regulatory compliance protocols, or the like), regulatory useprotocols, authentication protocols, authorization protocols, deliveryprotocols, activation protocols, encryption protocols, decryptionprotocols, and the like. Examples of a cryptographic logic include oneor more crypto-algorithms signal-bearing media, crypto controllers(e.g., crypto-processors), cryptographic modules (e.g., hardware,firmware, or software, or combinations thereof for implementingcryptographic logic, or cryptographic processes), and the like. See, forexample, Hosseini-Khayat, S., “A lightweight Security Protocoal forUltra-low Power ASIC Implementation for Wireless Implantable MedicalDevices,” 2011 Symposium on Medical Information and CommunicationTechnology (ISMICT), pages 6-9, 27-30 Mar. 2011, and Rasmussen, K. R.,et al., “Proximity-based Access Control for Implantable MedicalDevices,” CCS '09, Proceedings of the 16^(th) ACM Conference on Computerand Communications Security, Nov. 9-13, 2009, each of which isincorporated herein by reference.

FIG. 8 is a block diagram illustrating in greater detail variouscircuitry components of a lumen traveling device system including lumentraveling device control system 30. As discussed elsewhere herein, thecircuitry components of lumen traveling device control system 30 can belocated entirely on the lumen traveling device, or can be distributedbetween the lumen traveling device and one or more remote devices thatalong with the lumen traveling device form a lumen traveling devicesystem. Lumen traveling device control system 30 includes non-transitorymachine readable media 111, which stores instructions and/or data forimplementation of/use by control circuitry 800 and lumen travelingdevice control system 30. The control circuitry 800 of the lumentraveling device control system 30 is operationally linked to one ormore sensor(s) 802. At least a portion of the one or more sensor(s) 802are associated with the lumen traveling device, with a remote device, ora combination thereof. The signal generated by sensor(s) 802 may betransmitted to sensing circuitry 804, a component of control circuitry800. Sensor(s) 802 can include arrival sensor 805 a for detectingarrival of the lumen traveling device at a branch point in the body tubetree. Alternatively, or in addition, sensing circuitry 804 can includeall or a portion of arrival sensor 805 b, which may be, for example,processing circuitry configured to process signals from sensor(s) 802 todetermine arrival of the lumen traveling device at a branch point in thebody tube tree. In addition to sensing circuitry 804, the controlcircuitry 800 of the lumen traveling device control system 30 mayinclude response control circuitry 806, motion control circuitry 808,and mapping circuitry 810. Response control circuitry 806 provides aresponse control signal to active portion 812. Motion control circuitry808 provides control of propelling mechanism 822, and optionallysteering mechanism 824 and/or motion arresting portion 826. Mappingcircuitry 810 is operatively connected to motion control circuitry 808and configured to control movement in the body tube tree based at leastin part on a map of the body tube tree. Control circuitry 800 alsoincludes data storage portion 814, which can, for example, be used tostore pattern data 816 or pattern variables 818 for determining anactivation pattern of active portion 812. Data storage portion 814 canalso store map data 820, including, for example, a map of some or all ofthe relevant body tube tree(s) of the subject, the location of one ormore target locations or landmarks on the map, and/or the currentlocation of the lumen traveling device relative to the map. Map data 820stored in data storage portion 814 can also include data relating to oneor more pre-determined motion patterns for use by mapping circuitry 810and motion control circuitry 808 to control movement of the lumentraveling device in a pre-determined pattern. Control circuitry 800further includes transceiver circuitry 828, which provides for thetransmission and reception of data and/or power signals between thelumen traveling device and one or more remote devices or externaldevices (e.g., monitoring or recording equipment). Control circuitry 800can optionally include one or more timing device 827, which can be onboard a lumen traveling device or on a remote device, e.g., as depictedin FIG. 7. In some embodiments, control circuitry 800 may alternatively,or in addition, receive a timing signal containing information relatingto an absolute or relative time measure from a remote source. A timingsignal may be received by sensor(s) 802, or by transceiver circuitry828. Optionally, transceiver circuitry 828 can also receive one or moreposition indicator signal from position indication source(s) 829, whichmay be a radiologic source 829 a, an ultrasonic source 829 b, anelectromagnetic source 829 c (including but not limited to an RF beacon,a cellular communication source, a satellite communication source, aGPS, a personal area network, or a body area network), or a magneticsource 829 d, for example. A user input portion 830 provides for theinput of user instructions, parameters, and/or external data to controlcircuitry 800. Finally, one or more power source 832 is configured toprovide power to at least one of the sensor, control circuitry,propelling mechanism, steering mechanism, motion arresting portion, andactive portion. Some components of the lumen traveling device can beoperated in whole or in part under software control, and controlcircuitry 800 can include hardware, software, firmware, or variouscombinations thereof. The lumen traveling device can include componentsthat are primarily hardware-based, e.g., sensor 802, active portion 812,propelling mechanism 822, steering mechanism 824, motion arrestingportion 826 and, optionally, user input portion 830. Hardware-baseddevices can include components that are electrical, mechanical,chemical, optical, electromechanical, electrochemical, electro-optical,and are not limited to the specific examples presented herein. Asdescribed elsewhere, portions of the control circuitry, including, forexample, the motion control circuitry, the response control circuitry,and the mapping circuitry can be located entirely in or on thestructural element of the lumen traveling device or can be located inpart associated in a remote device.

A power source 832 as depicted in FIG. 8 can include one or more of abattery or microbattery, a fuel cell or biofuel cell, or a nuclearbattery. One or more power sources of the same or different types can beincluded in the lumen traveling device, without limitation. Batteriescan be located on the lumen traveling device, possibly a microbatterylike those available from Quallion LLC (Sylmar, California) or of thetype designed as a film (U.S. Pat. Nos. 5,338,625 and 5,705,293), eachof which is incorporated herein by reference. Alternatively, the powersource could be one or more fuel cell such as an enzymatic, microbial,or photosynthetic fuel cell or other biofuel cell (US2003/0152823A1;WO03/106966A2; or Chen, T. et al., J. Am. Chem. Soc., 2001,123:8630-8631, each of which is incorporated herein by reference), andcould be of any size, including the micro- or nano-scale. In anembodiment, the power source can include laterally packagedpiezoelectric fine wires that convert biomechanical energy (e.g.,stretching muscles, beating heart, walking) into electrical energy usinga nanogenerator (see, e.g., Yang et al., Nature Nanotechnol., 2009,4:34-39 or Yang et al., Nano Lett., 2009, 9:1201-1205, each of which isincorporated herein by reference). In another embodiment, the powersource can include a pressure-rectifying mechanism that utilizespulsatile changes in blood pressure or an acceleration-rectifyingmechanism as used in self-winding watches, or other types offlow-rectifying mechanism capable of deriving energy from other flowparameters. In an embodiment, the power source can be a nuclear battery(see, e.g., Wacharasindhu et al., Appl. Phys. Lett., 2009, 95:014103,which is incorporated herein by reference).

In an embodiment, the power source can be located remote from thestructural element and can include an electrical power source connectedto the structural element by a wire, an optical power source connectedto the structural element by a fiber-optic line or cable, or a powerreceiver capable of receiving power from an acoustic source orelectromagnetic source (e.g., infrared energy, or inductively coupled,as described in U.S. Pat. Nos. 6,170,488, and 7,212,110; U.S. PatentApplication No. 2005/0228259; and Budgett et al., J. Appl. Physiol.,2007, 102:1658-1663, each of which is incorporated herein by reference).In an embodiment, the lumen traveling device can include a powertransmitter capable of transmitting power (e.g., acoustic power,electrical power, or optical power) from the lumen traveling device to asecondary location. The secondary location can be, for example, anotherdevice within the body, either in a body lumen or elsewhere, whichincludes a power receiver and structures for using, storing and/orre-transmitting the received power. A remote device of a lumen travelingdevice system can include its own power supply, whether or not itsupplies power to a lumen traveling device.

The lumen traveling device control system of the lumen traveling device,including on-board and/or remote control circuitry, as depicted in FIG.8 can be implemented at least in part in the form of logic, includinganalog or digital logic circuitry and software, or a combinationthereof. FIG. 9 depicts logic modules (which may include software orhardware) for use in lumen traveling device control system 30 asdescribed herein. As shown in FIG. 9, logic 900 for controlling a lumentraveling device, can include, for example, a sensing module 902 capableof processing an input from a sensor 904 on the lumen traveling deviceto generate a sense signal indicating detection of a parameter value inthe lumen of a body tube tree of an organism; a response control module906 capable of receiving and processing the sense signal from thesensing module 902 and based at least in part upon the sense signalgenerating a response control signal configured for causing an action tobe performed in the lumen of the body tube tree by an active portion 908of the lumen traveling device; and a motion control module 910 capableof generating a signal for controlling at least one of a propellingmechanism 912 and a steering mechanism 914 on the lumen traveling deviceto control direction or rate of movement of the lumen traveling devicethrough the body tube tree. The logic 900 for controlling a lumentraveling device can further include a mapping module 916 capable ofreceiving information from the sensing module 902 and configured tolocate the lumen traveling device on an existing map of the body tubetree or to generate a map de novo of the body tube tree based at leastin part upon the sense signal. The mapping module 916 is further capableof providing information to motion control module 910. Motion controlmodule 910 is capable of producing an analog or digital signal thatcontrols at least one of a propelling mechanism 912 and a steeringmechanism 914 on the lumen traveling device. Control of the direction orrate of movement of the lumen traveling device can be based at least inpart upon a map of the body tube tree. The mapping module 916 caninclude logic for constructing, extending, or refining at least one map,based on sensed parameter values and/or determining the location of thelumen traveling device on a map. Data storage portion 918, which may be,for example, a memory location on the lumen traveling device (like datastorage portion 814 in FIG. 8) can contain pattern data 920, patternvariables 922, and map data 924. Map data 924 can include datarepresenting a map generated by mapping module 916. Pattern data 920 andpattern variables 922 stored in data storage portion 918 can be used inthe generation of or for directing operation of at least one ofpropelling mechanism 912 and steering mechanism 914, and/or in thegeneration of response control signals used in the control of activeportion 908. For example, if the active portion 908 releases a drug,pattern data 920 can include a pattern for the rate of drug release overtime, e.g. with the pattern including an array of data points in whicheach data point represents the rate of drug release at a particulartime. Pattern variables 922 can include variables used for generating apattern of action taken by the active portion. For example, variablescan include duration and frequency of occurrence of pulses of drugrelease. Logic 900 may be implemented in digital circuitry; analogcircuitry, software, or combinations thereof.

Data storage portions (e.g., data storage portion 918 and data storageportion 814 and other data storage portions or structures describedelsewhere herein) can include various types of non-transitory machinereadable media 111 for use in a lumen traveling device control system.In addition, other portions of lumen traveling device control system 30,including logic 900, may be stored in or implemented in non-transitorymachine readable media 111, as depicted in FIG. 9.

Non-transitory machine readable media 111 as depicted in, e.g., FIGS. 2,7, 8, 9, and 10, can be located on-board lumen traveling device or atleast in part on a lumen traveling device and in part on one or moreremote device, e.g. as depicted in FIG. 7, and can include any mediathat can be accessed by control circuitry and logic of the lumentraveling device, and/or remote devices. By way of example, and not oflimitation, non-transitory machine readable media 111 can be computerreadable media. By way of further example, non-transitory machine 111readable media can be recordable-type media. Computer readable media mayalso be recordable-type media, and the qualities of being “computerreadable” and “recordable-type” should not be construed as beingmutually exclusive, though in some cases a computer readable media maynot be a recordable-type media, and vice versa. Machine readable mediainclude volatile and nonvolatile, removable and non-removable mediaimplemented in any method or technology for storage of information suchas machine readable instructions, data structures, program modules, orother data. Non-transitory machine readable media include, but are notlimited to, random-access memory (RAM), read-only memory (ROM),electrically erasable programmable read-only memory (EEPROM), flashmemory, or other memory technology, CD-ROM, digital versatile disks(DVD), or other optical disk storage, magnetic cassettes, magnetic tape,magnetic disk storage, or other magnetic storage devices, or any othermedia which can be used to store the desired information and which canbe accessed by control circuitry 800 and/or logic 900, and/or be used inthe implementation of logic 900. In a further embodiment, computerstorage media may include a group of computer storage media devices. Inan embodiment, machine readable media may include an information store.In an embodiment, an information store may include a quantum memory, aphotonic quantum memory, or atomic quantum memory. Combinations of anyof the above may also be included within the scope of non-transitorymachine readable media. Machine readable media can be located on a lumentraveling device configured for placement in a body lumen. In anembodiment, machine readable media can be located at least in part on alumen traveling device and at least in part on and one or more remotedevices configured to perform at least some of the functionalities ofthe lumen traveling device control system 30, e.g. as depicted in anddescribed in connection with FIG. 7.

Communication media may embody machine readable instructions, datastructures, program modules, or other data in a modulated data signalsuch as a carrier wave or other transport mechanism and include anyinformation delivery media. The term “modulated data signal” means asignal that has one or more of its characteristics set or changed insuch a manner as to encode information in the signal. By way of example,and not limitation, communication media may include wired media, such asa wired network and a direct-wired connection, and wireless media suchas acoustic, RF, optical, and infrared media. Examples of communicationmedia include digital and/or analog communication media (e.g., a fiberoptic cable, a waveguide, a wired communications link, or a wirelesscommunication link (e.g., transmitter, receiver, transmission logic,reception logic, etc.), etc.). Communication media can carry databetween portions or components of a lumen traveling device, between alumen traveling device and one or more remote devices, and/or betweentwo or more remote devices. In some embodiments, machine readableinstructions, data structures, program modules, or other data used inmethods and systems as described herein can be implemented ordistributed via communication media.

In a general sense, the various aspects described herein can beimplemented, individually and/or collectively, by a wide range ofhardware, software, firmware, and/or any combination thereof can beviewed as being composed of various types of “electrical circuitry.”Consequently, as used herein “electrical circuitry” includes, but is notlimited to, electrical circuitry having at least one discrete electricalcircuit, electrical circuitry having at least one integrated circuit,electrical circuitry having at least one application specific integratedcircuit, electrical circuitry forming a general purpose computing deviceconfigured by a computer program (e.g., a general purpose computerconfigured by a computer program which at least partially carries outprocesses and/or devices described herein, or a microprocessorconfigured by a computer program which at least partially carries outprocesses and/or devices described herein), electrical circuitry forminga memory device (e.g., forms of memory (e.g., random access, flash, readonly, etc.)), and/or electrical circuitry forming a communicationsdevice (e.g., a modem, communications switch, optical-electricalequipment, etc.). The subject matter described herein may be implementedin an analog or digital fashion or some combination thereof.

In some embodiments described herein, logic and similar implementationsmay include software or other control structures suitable for operatingthe lumen traveling device. Electrical circuitry, for example, mayinclude one or more paths of electrical current constructed and arrangedto implement various logic functions as described herein. In someembodiments, one or more non-transitory machine readable media for usein a lumen traveling device control system are configured to bear animplementation detectable by a lumen traveling device including, forexample, an instruction set for a lumen traveling device. In someembodiments, the non-transitory machine readable media is carried by thelumen traveling device. In other embodiments, the non-transitory machinereadable media is carried in part by the lumen traveling device and inpart by a remote device. The non-transitory machine readable media caninclude but is not limited to computer readable media, including, forexample, non-volatile memory (e.g., ROM, PROM, EPROM, EEPROM, and Flashmemory). In some variants, an implementation may include special-purposehardware, software, firmware components, and/or general-purposecomponents executing or otherwise invoking special-purpose components.Logic and/or other implementations for operating a lumen travelingdevice can include logic and/or other implementations relating to updateor other modification of existing software or firmware, or of gatearrays or other programmable hardware, by a reception of or atransmission of one or more instructions in relation to one or moreoperations of a lumen traveling device and/or remote device as describedherein.

In some embodiments, logic and similar implementations may includeexecuting a special-purpose instruction sequence or otherwise invokingcircuitry for enabling, triggering, coordinating, requesting, orotherwise causing one or more occurrences of any of the sensing,responding, performing, moving and mapping operations of the lumentraveling device as described herein. In some variants, operational orother logical descriptions may be expressed directly as source code andcompiled or otherwise used as an executable sequence of instructions. Insome embodiments, for example, C++ or other code sequences can becompiled directly or otherwise implemented in high-level descriptorlanguages (e.g., a logic-synthesizable language, a hardware descriptionlanguage, a hardware design simulation, and/or other such similarmode(s) of expression). Alternatively or additionally, some or all ofthe logical expression may include Verilog-type hardware description orother circuitry model before physical implementation in hardware.

In an embodiment shown in FIG. 10, lumen traveling device control system30 includes motion control module 910 capable of controlling at leastone of a propelling mechanism 912 and a steering mechanism 914 on thelumen traveling device based at least in part upon a motion controlsignal from a remote control system 901. Otherwise, the logic 950 islike that shown in FIG. 9, including sensing module 902 capable ofprocessing an input from a sensor 904 on the lumen traveling device togenerate a sense signal indicating detection of a parameter value in alumen of a body tube tree of an organism; a response control module 906capable of receiving the sense signal from the sensing module 902 andbased at least in part upon the sense signal generating a responsecontrol signal configured for causing an action to be performed in thelumen of the body tube tree by an active portion 908 of the lumentraveling device; a motion control module 910 capable of controlling atleast one of a propelling mechanism 912 and a steering mechanism 914 onthe lumen traveling device to control direction or rate of movement ofthe lumen traveling device through the body tube tree; and a mappingmodule 916 capable of receiving data from a sensing module 902 andinforming a motion control module 910 regarding the current location ofthe lumen traveling device on a map of a body tube tree. The mappingmodule 916 can further include control logic that uses a pre-programmedpattern which may be stored in a memory location on the lumen travelingdevice (like data storage portion 814 in FIG. 8). The logic 950 caninclude a data storage portion 918 that includes pattern data 920,pattern variables 922, and map data 924. The remote control system 901may be operated by an operator such as, for example, a medicalcaregiver. In some embodiments, the remote control system 901 may beunder complete control of remote device such as, for example, a generalcomputer or microprocessor that receives data from the lumen travelingdevice, processes the data, and transmits an appropriate set ofoperational instructions to the lumen traveling device based on the datareceived. Logic and other aspects of lumen traveling device controlsystem 30 can be stored in/implemented in non-transitory machinereadable media 111 included in the lumen traveling device and/or remotecontrol system 901.

At least a portion of the devices and/or processes described herein canbe used in connection with an image processing system. A typical imageprocessing system generally includes one or more of a system unithousing, a video display device, memory such as volatile or non-volatilememory, processors such as microprocessors or digital signal processors,computational entities such as operating systems, drivers, applicationsprograms, one or more interaction devices (e.g., a touch pad, a touchscreen, an antenna, etc.), control systems including feedback loops andcontrol motors (e.g., feedback for sensing lens position and/orvelocity; control motors for moving/distorting lenses to give desiredfocuses). An image processing system may be implemented utilizingsuitable commercially available components, such as those typicallyfound in digital still systems and/or digital motion systems.

In some embodiments, the lumen traveling device may be used inconnection with a data processing system. The data processing system mayinclude one or more of a system unit housing, a video display device,memory such as volatile or non-volatile memory, processors such asmicroprocessors or digital signal processors, computational entitiessuch as operating systems, drivers, graphical user interfaces, andapplications programs, one or more interaction devices (e.g., a touchpad, a touch screen, an antenna, etc.), and/or control systems includingfeedback loops and control motors (e.g., feedback for sensing positionand/or velocity; control motors for moving and/or adjusting componentsand/or quantities). A data processing system may be implementedutilizing suitable commercially available components, such as thosetypically found in data computing/communication and/or networkcomputing/communication systems.

The functionalities of the lumen traveling device control system can bedistributed between hardware, firmware, and software located at two ormore sites. An electrical circuitry portion of the lumen travelingdevice control system can include, but is not limited to, electricalcircuitry associated with the sensor, control circuitry, and electronicsassociated with the propelling mechanism, steering mechanism, motionarresting portion, and active portion. While the control circuitry hasbeen discussed within the context of electrical circuitry, it will beappreciated that in some embodiments other types of logic/circuitry canbe used in place of or in addition to electrical circuitry, and thecontrol circuitry described herein is not limited to electricalcircuitry. For example, fluid circuitry, chemo-mechanical circuitry, andother types of logic/circuitry can provide equivalent functionality.

The lumen traveling device with control circuitry, logic and othercomponents described herein can be part of a system that includesnon-transitory machine readable media for use in a lumen travelingdevice control system including one or more instructions that cause thelumen traveling device control system to operate the lumen travelingdevice in the body tube tree of a subject.

FIG. 11 illustrates a block diagram of a system 1100 that includes a setof instructions 1104 for operating a lumen traveling device. Anembodiment of system 1100 is provided using non-transitory machinereadable media for use in a lumen traveling device control system 1102including a set of instructions 1104 including one or more instructionsthat cause the lumen traveling device control system to activate apropelling mechanism on a lumen traveling device to propel the lumentraveling device within a body tube tree; one or more instructions thatcause the lumen traveling device control system to determine an arrivalof the lumen traveling device at a branch point in the body tube treebased upon a signal from at least one arrival sensor on the lumentraveling device, the branch point including at least two branchchannels; one or more instructions that cause the lumen traveling devicecontrol system to select one of the at least two branch channelssubstantially randomly; one or more instructions that cause the lumentraveling device control system to direct the propelling mechanism onthe lumen traveling device to move the lumen traveling device into theselected branch channel; one or more instructions that cause the lumentraveling device control system to store information regarding at leastone of the at least two branch channels; one or more instructions thatcause the lumen traveling device control system to direct the sensing ofa local parameter value from a parameter sensor on the lumen travelingdevice; and one or more instructions that cause the lumen travelingdevice control system to direct an active portion of the lumen travelingdevice to perform an action based at least in part upon the localparameter value. The one or more instructions can be, for example,computer executable and/or logic-implemented instructions. Thenon-transitory machine readable media 1102 can include computer readablemedia 1106, or recordable-type media 1108, for example.

The system described herein includes non-transitory machine readablemedia for use in a lumen traveling device control system including oneor more instructions relating to operation of a lumen traveling devicein a body tube tree. In an embodiment, the non-transitory machinereadable media is carried by the lumen traveling device. In a furtherembodiment, the non-transitory machine readable media is carried in partby the lumen traveling device and in part by a remote device. Thenon-transitory machine readable media can include computer readablemedia, which may be, for example, recordable-type media. In someinstance, the non-transitory machine readable media carried by the lumentraveling device can include non-volatile memory selected from a ROM,PROM, EPROM, EEPROM, Flash memory, or the like.

FIG. 12 illustrates the steps for a method 1200 of operating a lumentraveling device. The method includes activating a propelling mechanismon the lumen traveling device to propel the lumen traveling devicewithin a body tube tree at 1202; detecting an arrival of the lumentraveling device at a branch point in the body tube tree with at leastone arrival sensor on the lumen traveling device, the branch pointincluding at least two branch channels at 1204; selecting one of the atleast two branch channels substantially randomly at 1206; causing thepropelling mechanism on the lumen traveling device to move the lumentraveling device into the selected branch channel at 1208; storinginformation regarding at least one of the at least two branch channelsat 1210; sensing a local parameter value with a parameter sensor on thelumen traveling device at 1212; and performing an action with an activeportion of the lumen traveling device based at least in part upon thelocal parameter value at 1214. The method of FIG. 12 can be performedunder the control of control circuitry such as that depicted in FIG. 8.

The method of operating a lumen traveling device with a lumen travelingdevice control system includes one or more instructions for activating apropelling mechanism on the lumen traveling device. The one or moreinstructions for activating a propelling mechanism can originate fromthe motion control circuitry of the lumen traveling device and/or anassociated remote device. The instructions can include but are notlimited to, stop instructions, go instructions, speed up instructions,and/or slow down instructions. In an embodiment, the motion controlcircuitry is operatively connected to one or more steering mechanisms.Instructions originating from the motion control circuitry includeinstructions to the steering mechanism and include but are not limitedto, instructions to turn right, turn left, turn a certain number ofdegrees, reverse, go up, go down, or a combination thereof. Movementscan be defined relative to an axis (e.g., of the lumen traveling device,of the lumen, of the direction of travel, or the body of the subject) orrelative to some other relative or absolute frame of reference. Thepropelling mechanism and the steering mechanism are activated by themotion control circuitry in response to signals received from one ormore sensors associated with the lumen traveling device.

The lumen traveling device can include one or more sensors configured tosense one or more local parameter values in the lumen of a body tubetree. In an embodiment, the one or more local parameters can include abranch point in the body tube tree. The arrival of the lumen travelingdevice at a branch point in the body tube tree can be detected with oneor more specialized arrival sensors. The one or more arrival sensors caninclude, but are not limited to, pressure sensors, temperature sensors,flow sensors, viscosity sensors, shear sensors, pH sensors, chemicalsensors, optical sensors, acoustic sensors, biosensors, electricalsensors, magnetic sensors, clocks or timers. An arrival sensor can beconfigured to sense one or more parameter values characteristic of abranch point in a body tube tree. Examples of parameter valuescharacteristic of a branch point in a body tube tree include but are notlimited to changes in flow and/or pressure within the channel at thebranch point (e.g., turbulence, eddies, etc.), changes in chemicalcomposition at the branch point, interaction with and detection of asolid surface portion of the branch point (e.g., at a T-junctionintersection or apex of the branch point) by either physically bouncingoff the solid surface or bouncing a signal off of the surface, e.g.,reflection of electromagnetic wave, ultrasonic echoes, etc. As usedherein, an “arrival sensor” can include not only a sensor but alsocircuitry or logic for performing signal processing or analysis forsensing arrival of the lumen traveling device at a branch point.

In an embodiment, the arrival sensor can be a charged coupled device(CCD), a complementary metal oxide semiconductor (CMOS) or other imagecapturing sensor on the lumen traveling device which captures images ofthe body tube tree at specified time and/or distance intervals as thelumen traveling device travels through the lumen of the body tube tree,used in combination with image analysis hardware and/or software. Imageanalysis can be used to recognize an image of a branch point (e.g.,bifurcation, trifurcation, other) relative to an image of the lumen ofthe body tube tree.

In an embodiment, the arrival sensor can measure changes in flow andpressure of fluid or gas in a body tube tree. The flow of fluid or gasin a body tube tree is disrupted at branch points or bifurcations. Inthe arterial vasculature, for example, these disruptions are observed asturbulence, eddies, flow separation, stasis and transient flow reversalsat various regions in proximity to the branch point (see, e.g., Motomiya& Karino, Stroke, 1984, 15:50-56 and Karino et al., Ann. NY Acad. Sci.,1987, 516:422-441, each of which is incorporated herein by reference).These disruptions can be measured as changes in pressure and flowrelative to pressure and flow measured in a non-bifurcated portion ofthe body tube tree. These relative changes can be used to identify abranch point. Examples of intravascular pressure and flow sensors havebeen described in U.S. Pat. No. 6,053,873 and U.S. Pat. No. 5,873,835 aswell as in Schnakenberg et al., Sensors and Actuators A: Physical, 2004,110: 61-67, each of which is incorporated herein by reference. Thearrival sensor can include one or more anemometer-type flow transducerfor measuring air flow in, for example, the bronchial body tube tree.Examples of microscale anemometer-type sensors are described in U.S.Pat. No. 7,451,537 and in Wang et al., Sensors, 2007 7:2389-2401, whichis incorporated herein by reference. In an embodiment, the arrivalsensor can be an ultrasonic sensor. In this instance, the lumentraveling device emits ultrasonic waves which reflect off surfaces inthe path of the lumen traveling device, including lumen walls and branchpoints within the body tube tree. An example of a microscale ultrasonicsensor is described in Hirsch et al., J Physics: Conf. Series, 2006,34:475-480, which is incorporated herein by reference.

In an embodiment, the lumen traveling device can move substantiallyrandomly into one of two or more branch channels. As used herein,“moving substantially randomly” means powered and/or directed movementof lumen traveling device in which the direction of travel is selectedat random from among two or more possible directions of travel.Selection of the direction of travel can be determined by controlcircuitry on the lumen traveling device or a remote device. For example,supposing the lumen traveling device has arrived at a branch pointincluding two branch channels, so that there are two possible directionsof travel to select from, the control circuitry can generate a randomnumber that may be either even or odd. The first of the two possibledirections of travel is selected if the random number is even, and thesecond of two possible directions of travel is selected if the randomnumber is even. It will be appreciated that, while in the foregoingexample a selection is made between two possible directions of travel, arandom selection can be made from among more than two possibledirections of travel, based upon suitable processing of a randomlygenerated number.

As the lumen traveling device moves through a branch channel of a bodytube tree, information is collected regarding the properties of thebranch channel and its surroundings using one or more sensors.Information collected by the lumen traveling device relating toproperties of a branch channel can include but is not limited to thedirection or orientation of the branch channel relative to some fixedpoint (e.g., point of origin, internal or external reference points) orother branched channels; the length of the branch channel; thestructural configuration of the branch channel (e.g., straight, curved,a combination thereof); the branching pattern of the branch channel; thedistance from one branch point to the next branch point; the luminaldimension of the branch channel; and the proximity of the branch channelto a valve or other channel restriction.

The distance traveled by the lumen traveling device can be measuredusing an odometer type sensor. In an embodiment, the odometer is amechanical type odometer with a rotating element such as, for example, awheel or a motor. For example, the lumen traveling device can include awheel-like attachment that engages the surface of the lumen of the bodytube tree and rotates with the movement of the device. The knowncircumference of the wheel and the number of rotations can be used toestimate the distance traveled by the lumen traveling device. In anembodiment, the rotating element can be a rotary-type motor componentassociated with the lumen traveling device. In a further embodiment, theodometer can calculate distance traveled using an image sensor tocapture images at set intervals and measuring displacement betweencaptured images as described in U.S. Pat. No. 7,171,285, which isincorporated herein by reference.

The dimensions of the lumen of a branch channel can be measured usingelectromagnetic radiation wherein the lumen traveling device isconfigured to emit a transverse ring of electromagnetic radiation whichbecomes incident upon a discrete cross section of the interior surfaceof the lumen and is visualized as a ring of electromagnetic radiationreflected back from the luminal surface as described in U.S. Pat. No.5,381,786 which is incorporated herein by reference. The dimensions ofthe lumen of a branch channel can also be measured using an expandablestructure such as a spiral coil or inflatable balloon as described inU.S. Pat. No. 6,175,757, which is incorporated herein by reference.

Information relating to properties of one of the two or more branchchannels traveled by the lumen traveling device, including direction ororientation of the branch channel, length of the branch channel, thestructural configuration of the branch channel, the branching pattern ofthe branch channel, the distance from one branch point to the nextbranch point, the luminal dimension of the branch channel, and theproximity of the branch channel to a valve or other channel restriction,can be stored in one or more data storage locations within the lumentraveling device. In a further embodiment, information relating toproperties of one of the two or more branch channels traveled by thelumen traveling device is transmitted to and stored in one or more datastorage locations of one or more remote devices in communication withthe lumen traveling device. The information relating to properties ofone of the two or more branch channels can be stored on non-transitorymachine readable media, such as one or more recordable-type media (e.g.,floppy disk, a hard disk drive, a compact disc, digital video, a digitaltape, a computer memory); and/or non-volatile memory (e.g., ROM, PROM,EPROM, EEPROM, or Flash memory).

In addition to information relating to the properties of at least one ofthe two or more branch channels traveled by the lumen traveling device,information relating to the relative location of the lumen travelingdevice is collected. Information relating to the relative location ofthe lumen traveling device as well as information relating to propertiesof the branch channels can be used to generate a map of a body tube treeand/or to place the lumen traveling device on a pre-existing map of thebody tube tree. In an embodiment, the location of the lumen travelingdevice can be determined based on sensing a position indicator signal.In an embodiment, the position indicator signal can be at least onesignal from an inertial navigation system associated with the lumentraveling device. Miniaturized inertial navigation systems usingmicroelectromechanical (MEMS) accelerometers and gyroscopes have beendescribed (see, e.g., U.S. Pat. No. 5,313,835; U.S. Patent Application2008/0121054; Lynch et al., J Aerospace Eng., 3:108-114, 2003; andFoxlin et al., “Miniature 6-DOF inertial system for tracking HMDs,” SPIEvol. 3362, Helmet and Head-Mounted Displays III, AeroSense 98, Orlando,Fla., Apr. 13-14, 1998, each of which is incorporated herein byreference). The inertial navigation system can be combined with one ormore other position indicator signal such as, for example, one or moreglobal position system (GPS) signal (see, e.g., Brown et al.,“Performance test results of an integrated GPS/MEMS inertial navigationpackage,” Proceedings of ION GNSS 2004, Long Beach, Calif., September2004, which is incorporated herein by reference).

In an embodiment, the position indicator signal can originate from aremote source. Examples of position indicator signals originating fromone or more remote sources include but are not limited to radiologicalsignals, ultrasonic signals, magnetic signals, and electromagneticsignals. Further examples of position indicator signals include aradiofrequency (RF) signal, a global positioning system (GPS) signal, asignal from a personal area network (PAN), or a signal from a body areanetwork (BAN). A body area network can function generally as described,for example, in Jovanov, E., Milenkovic, A., Otto, C., and de Groen, P.,“A wireless body area network of intelligent motion sensors for computerassisted physical rehabilitation,” J. of NeuroEngineering andRehabilitation, 2:6, Mar. 1, 2005, which is incorporated herein byreference. The signal can originate from a single remote source or aplurality of signals can originate from a plurality of remote sources.Signal sources that produce radiological signals, ultrasonic signals,magnetic signals, electromagnetic signals, RF, GPS signals known tothose of skill in the relevant arts and are examples of remote sources.A position indicator signal can be received by a receiver on the lumentraveling device that is also used to receive data and/or power from aremote device (e.g., receiver/transmitter 134 in FIG. 7) or a positionindicator signal can be received by a separate receiver.

In an embodiment, time of flight and or pulse measurements can be usedto determine the current location of a lumen traveling device within abody tube tree. Time of flight measurements or pulse measurements arebased on measuring the time of flight of a signal, e.g., a positionindicator signal, from the measurement device to a target and backagain. Trilateration is the technique of determining the position of atarget by calculating the time of arrival from at least three differentlocations (i.e., readers). Multilateration, also known as hyperbolicpositioning, is the process of locating a target by accurately computingthe time difference of arrival of a signal emitted from the target tothree or more receivers. It also refers to the case of locating areceiver by measuring the time difference of arrival of a signaltransmitted from three or more synchronized transmitters. Alternatively,a triangulation method can be used to determine the current location ofthe lumen traveling device based on the plurality of position indicatorsignals from a plurality of remote sources. Triangulation, also calledangle of arrival, is the process of finding the coordinates and thedistance to a point by calculating the length of one side of a triangle(which is formed by that point and two other known reference points),based on measurements of the angles and the length of the sides of thetriangle.

In an embodiment, the position indicator signals can be one or moreradiofrequency signals. For example, the lumen traveling device caninclude one or more radiofrequency identification (RFID) tags.Miniaturized RFID tags with dimensions of 50 microns by 50 microns havebeen described by Burke & Rutherglen, Biomed Microdevices, Jan. 24, 2009(Epub ahead of print), which is incorporated herein by reference. Anexample of implantable device with an RFID tag has been described inU.S. Pat. No. 7,596,403, which is incorporated herein by reference.Radiofrequency signals can also be used for navigation, as described,for example, in U.S. Patent Application 2008/0266106 and Mehmood et al.,“Autonomous navigation of mobile agents using RFID-enabled spacepartitions,” ACMGIS '08, Nov. 5-7, 2008, Irvine, Calif., USA, each ofwhich is incorporated herein by reference. Navigation systems usingultrasound have been described in U.S. Patent Application 2009/0062646and Eulenstein et al., “Ultrasound-based navigation system incorporatingpreoperative planning for liver surgery,” International Congress SeriesCARS 2004—Computer Assisted Radiology and Surgery, Proceedings of the18^(th) International Congress and Exhibition, 2004, 1268:758-763, eachof which is incorporated herein by reference. Navigation systems usingmagnetic field have been described in U.S. Pat. Nos. 6,776,165 and4,658,214, each of which is incorporated herein by reference.

The lumen traveling device can be modified in such a way as to aide indetermining the current location of the lumen traveling device in a bodytube tree. In an embodiment, the lumen traveling device can include oneor more labels, markers or tags detectable by an external imaging systemor by a sensing device or structure within the body of the subject.Imaging of a body tube tree using an external imaging system can becombined with imaging of the lumen traveling device to provide a currentlocation for the lumen traveling device within the body tube tree.

In an embodiment, at least a portion of the lumen traveling device canbe constructed from a radiopaque metal capable of blocking radiation sothat the lumen traveling device is visible in a body tube tree by x-rayimaging. In a further embodiment, the lumen traveling device can be atleast partially coated with a radiopaque dye or contrast media. Examplesof contrast agents, radiopaque dyes, and roentgenographic drugs used forx-ray imaging and computed tomography (CT) scans include, but are notlimited to, barium sulfate and various iodine derivatives includingdiatrizoate meglumine, diatrizoate sodium, iodipamide meglumine,diatrizoic acid, ethiodized oil, iodipamide, iodixanol, iohexyl,iomeprol, iopamidol, iopanoic acid, iophendylate, iopromide, iothalamatemeglumine, iothalamate sodium, iothalamic acid, ioversol, ioxaglatemeglumaine, and ioxaglate sodium.

In an embodiment, the lumen traveling device can be at least partiallycoated with one or more of a contrast agent used for magnetic resonanceimaging (MRI) as exemplified by paramagnetic and supramagnetic agentswith one or more unpaired electrons, typically including manganese,iron, or gadolinium in their structure. Examples of MRI contrast agentscontaining iron include, but are not limited to, ferumoxides (magnetitecoated with dextran), ferumoxsil (magnetite coated with siloxane),ferumoxytol, ferumoxtran, ferucarbotran (RESOVIST), ferric chloride, andferric ammonium citrate. Examples of MRI contrast agents containinggadolinium include, but are not limited to, gadopentetate dimeglumine(Gd-DTPA; MAGNEVIST), gadobutrol (GADOVIST), gadodiamide (Gd-DTPA-BMA;OMNISCAN), gadoteridol (PROHANCE), Gd-DOTA (DOTAREM), gadofosvesettrisodium (VASOVIST), gadoversetamide (OPTIMARK), and gadobenatedimeglumine (MULTIHANCE). Examples of MRI contrast agents containingmanganese include but are not limited to mangafodipir trisodium(TESLASCAN) and EVP 1001-1.

In an embodiment, the lumen traveling device can include one or more ofa radioactive element used for diagnostic positron emission tomography(PET), single photon emission computed tomography (SPECT), or gammacamera imaging. Radioisotopes commonly used for PET, SPECT and gammacamera imaging include, but are not limited to, carbon-11; nitrogen-13;oxygen-15; and fluorine-18; salts of radioisotopes such as I-131 sodiumiodide, Tl-201 thallous chloride, Sr-89 strontium chloride; technetiumTc-99m; compounds containing iodine-123, iodine-124, iodine-125, andiodine-131; compounds containing indium-111 such as¹¹¹In-1,4,7,10-Tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid and¹¹¹In-Diethylenetriamine pentaacetic acid;¹⁷⁷Lu-[(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaaceticacid) (¹⁷⁷Lu-CHX-A″-DTPA), ⁶⁴Cu-DOTA, ⁸⁹Zr, and ⁸⁶Y-DOTA.

In an embodiment, the lumen traveling device can be at least partiallycoated with one or more agents used for diagnostic fluorescence imagingincluding, but not limited to, fluorescein (FITC), indocyanine green(ICG) and rhodamine B. Examples of other fluorescent dyes for use influorescence imaging include but are not limited to cyanine dyes such asCy5, Cy5.5, and Cy7 (Amersham Biosciences, Piscataway, N.J., USA) and/orAlexa Fluor dyes such as Alexa Fluor 633, Alexa Fluor 635, Alexa Fluor647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700 and Alexa Fluor750 (Molecular Probes-Invitrogen, Carlsbad, Calif., USA; see, e.g., U.S.Pat. App. No. 2005/0171434, incorporated herein by reference).Additional fluorophores include IRDye800, IRDye700, and IRDye680(LI-COR, Lincoln, Nebr., USA), NIR-1 and 1C5-OSu (Dejindo, Kumamoto,Japan), LaJolla Blue (Diatron, Miami, Fla., USA), FAR-Blue, FAR-GreenOne, and FAR-Green Two (Inn osense, Giacosa, Italy), ADS 790-NS and ADS821-NS (American Dye Source, Montreal, CA), NIAD-4 (ICx Technologies,Arlington, Va.). Other fluorescing agents include BODIPY-FL, europium,green, yellow and red fluorescent proteins, and luciferase. Quantum dotsof various emission/excitation properties are also available forfluorescence imaging (see, e.g., Jaiswal et al., Nature Biotech., 2003,21:47-51, which is incorporated herein by reference).

The non-transitory machine readable media of the system includes one ormore instructions for storing information derived from one or moreposition indicator signals. Information relating to one or more positionindicator signals representative of the current location of the lumentraveling device can be stored in one or more data storage locationswithin the lumen traveling device. Alternatively, information relatingto one or more position indicator signals representative of the currentlocation of the lumen traveling device can be transmitted to and storedin one or more remote devices associated with the lumen travelingdevice. Information relating to one or more position indicator signalsrepresentative of the current location of the lumen traveling device canbe stored on one or more recordable-type media (e.g., floppy disk, ahard disk drive, a compact disc, digital video, a digital tape, acomputer memory); or non-volatile memory (e.g., ROM, PROM, EPROM,EEPROM, or Flash memory).

Parameter sensors can include signal processing or analysiscapabilities; a sensed parameter value may be the parameter value ofinterest or the sensed parameter value may be a parameter valueindicative of a parameter value of interest, e.g., a parameter valuefrom which the parameter value of interest can be computed or derived.Information relating to a local parameter value can include, forexample, information regarding the presence, absence, quantity, rate ofchange, spatial or temporal pattern of distribution, or various othermeasures relating to or representative of a parameter of interest.

The lumen traveling device is further configured to sense and storeinformation relating to one or more local parameter values as the lumentraveling device travels through a body tube tree. The local parametercan include an anatomical feature such as, for example, a branch point,a valve, a growth, a plaque, a polyp, a tumor, a discoloration of thelumen wall, or other distinct feature of the lumen of the body tubetree. The local parameter can include a man-made structure such as animplantable device of some sort, potentially including another lumentraveling device. The local parameter can further include one or morechemical or physical marker or label previously placed into the lumen ofthe body tube tree by the lumen traveling device. Alternatively, thelocal parameter can include one or more of an electrical field, magneticfield, temperature, flow condition, time, location, pressure, pH,presence or concentration of a chemical compound or species, or objects,cells, cellular components. The local parameter can include an image.

Sensing a local parameter value can include sensing the presence of amaterial of interest in the fluid within the lumen of a body tube tree,or in or on the wall of the body tube tree. A material of interest inthe fluid can include, for example, an object such as a blood clot, athrombus, an embolus, a plaque, a lipid, a kidney stone, a dustparticle, a pollen particle, an aggregate, a cell, a specific type ofcell, a cell fragment, a cellular component, a platelet, an organelle, acollection or aggregation of cells or components thereof, a gamete, apathogen, or a parasite.

The lumen traveling device can include one or more parameter sensors forsensing a local parameter value. Parameter sensors are operativelyconnected to logic circuitry (hardware, firmware, and/or software) andcan be used to sense a local parameter value in or on the wall of thebody lumen, in the tissue that forms or surrounds the body lumen, or inthe fluid within the body lumen. A parameter sensor can be configured tomeasure various parameters, including, but not limited to, theelectrical resistivity of fluid, tissue, or other material, the densityof a material, the pH, the osmolality, or the index of refraction of thefluid at least one wavelength. Specific examples of a parameter sensorinclude a pressure sensor, a flow sensor, a temperature sensor, an imagesensor, a biosensor, and a chemical sensor. The selection of a suitableparameter sensor for a particular application or use site is consideredto be within the capability of a person having skill in the art. Aparameter sensor can further include some signal processing orpre-processing capability integrated therewith.

Information relating to a local parameter can be collected using one ormore sensing or information gathering devices or structures. The lumentraveling device can include one or more sensors of the same ordifferent types, including but not limited to pressure sensors,temperature sensors, flow sensors, viscosity sensors, shear sensors, pHsensors, chemical sensors, optical sensors, an image sensor, acousticsensors, biosensors, electrical sensors, magnetic sensors, clocks ortimers. Examples of sensors are provided in U.S. Pat. Nos. 5,522,394;5,873,835; 6,053,873; 6,409,674; 6,111,520; 6,278,379; 6,475,639;6,802,811; 6,855,115, and U.S. Patent Applications 2005/0277839 and2005/0149170, each of which is incorporated herein by reference.

Information relating to one or more local parameter values sensed by thelumen traveling device while traveling through a body tube tree can bestored in one or more data storage locations within the lumen travelingdevice. Alternatively, information relating to one or more localparameter values sensed by the lumen traveling device while travelingthrough a body tube tree can be transmitted to and stored in one or moreremote devices associated with the lumen traveling device. Informationrelating to one or more local parameter values sensed by the lumentraveling device while traveling through a body tube tree can be storedon one or more recordable-type media (e.g., floppy disk, a hard diskdrive, a compact disc, digital video, a digital tape, a computermemory); or non-volatile memory (e.g., ROM, PROM, EPROM, EEPROM, orFlash memory).

The block diagram in FIG. 13 summarizes the sensing and storing ofinformation 1300 related to the position or the environment of the lumentraveling device as it moves through the body tube tree of a subject.Sensing and storing information 1300 can include sensing one or moreposition indicator signals 1302; sensing one or more local parametervalues 1322; and storing information regarding at least one of the atleast two branch channels of the body tube tree at step 1346. Sensingone or more position indicator signals 1302 can further include one ormore of sensing a signal from an inertial navigation system 1304;sensing a magnetic signal originating from a remote source 1306; sensingan ultrasonic signal originating from a remote source 1308; sensing aradiological signal originating from a remote source 1310; and/orsensing an electromagnetic signal from a remote source 1312. Sensing anelectromagnetic signal from a remote source 1312 can further includesensing signals from one or more of an RF beacon 1314, a GPS 1316, awireless network 1317, a personal area network 1318, and/or a body areanetwork 1320. Sensing a position indicator signal can include sensing anencrypted signal 1319. Sensing one or more local parameter value 1322can include sensing one or more of concentration of analyte 1324; fluidflow 1326; temperature 1328; pressure 1330; acoustic signal 1332;optical signal 1334; electrical field 1336; magnetic field 1338; markeror label 1340; structure parameter 1342; electromagnetic field 1344, orimage 1345. Storing information regarding at least one of the at leasttwo branch channels 1346 of a body tube tree can include informationregarding one or more of direction 1348, orientation 1350, branchingpattern 1352, lumenal dimension 1354, length 1356, structuralconfiguration 1358, distance from another branch point 1360, andproximity to valve or channel restriction 1362. Information relating toposition indicator signals of a lumen traveling device, localparameters, and/or properties of branches of a body tube tree can bestored in one or more data storage locations within the lumen travelingdevice and/or stored in one or more remote devices. This information canbe used to generate a map of at least a portion of a body tube tree.

FIG. 14 illustrates generating a map 1400 of a body tube tree usingexploration and information related to the position and/or theenvironment of the lumen traveling device, including the steps ofestimating the current location of the lumen traveling device based onknown information (e.g., injection point, position indicator signal,existing map) at step 1402; moving in a direction chosen to maximize newinformation based on an estimate of known versus unknown locations atstep 1404; collecting and storing information relating to currentlocation based on exploration of local surroundings at step 1406 whereincollecting and storing information includes sensing properties of one ormore branches 1408, sensing one or more local parameters 1410, and/orsensing one or more position indicator signals 1412, as outlined in FIG.13; generating a local “sub”-map based on recorded data and movements atstep 1414; matching local sub-map to appropriate subset of the known mapusing known robotic mapping and localization techniques at step 1416;confirming and/or correcting map at step 1418; and updating informationregarding location of lumen traveling device on the map at step 1420.The steps of generating a map by localization and exploration can beimplemented in an iterative process 1422, which can be performed throughmultiple iterations as the lumen traveling device moves through thelumen of a body tube tree.

Information relating to the properties of the branch channels, theposition of the lumen traveling device, and local parameters can be usedto generate a map of at least a portion of a body tube tree. The map canbe based on information collected and stored by the lumen travelingdevice as it travels through the various branches of the body tube tree.The lumen traveling device can use ultrasonic, radio, microwave and/orlaser range finding to generate a map of the immediate environment ofthe device in the body tube tree. The lumen traveling device can useother sensors to perceive the immediate environment including but notlimited to cameras, radar, tactile sensors, compasses and globalpositioning (GPS). The lumen traveling device can be placed at theorigin of the map, and initial measurements taken at the origin aretaken to be the initial map of the body tube tree. The lumen travelingdevice can be instructed by the motion control circuitry to move in aspecific direction and to take another measurement. The new measurementcan be fit into the existing map on the assumption that the features inthe environment of the lumen traveling device have not changedsignificantly. The best fit returns a most likely location of the devicerelative to the origin; the measurements are then shifted by thedevice's now-known position, and contributed to the map. This cycle canbe repeated indefinitely as the lumen traveling device explores the bodytube tree. Measurements taken in the rearward direction of the device'spath of travel aide in localizing the device on the evolving map, whilemeasurements taken in the forward direction of the device's pathcontribute new information to the evolving map. See, e.g., Howell &Donald, Proceedings of the IEEE International Conference on Robotic andAutomation, 2000, ICRA '00, Apr. 24-28, 2000, 4:3485-3492, which isincorporated herein by reference.

In an embodiment, the map generated by exploration and localization canbe a metric map, a topographical map, or a combination thereof. See,e.g., Tomatis et al., Robotics Autonomous Systems, 44:3-14, 2003, whichis incorporated herein by reference. A metric map captures the geometricproperties of the environment traveled by an object and decomposes theproperties into a two-dimensional (2D) or three-dimensional (3D) latticeof grids or cells, with each cell representing the probability ofoccupancy. A topological map describes the connectivity of differentlocations within the environment. Topographical maps are graph-orientedmodels with nodes representing structural features of the environmentand vertices capturing adjacency and ordering information. In thisinstance, the structural features are the properties of the lumen sensedby the lumen traveling device as it travels through the body tube tree.A topological map may be computable from a metric map.

A number of map building algorithms have been described including butnot limited to probabilistic frameworks, Bayesian frameworks, artificialneural networks, Cartesian symbolic-oriented approaches, Markovlocalization, simultaneous localization and mapping (SLAM), concurrentmapping and localization (CML), and expectation maximization (see, e.g.,Thrun, “Robotic Mapping: A Survey,” In Exploring Artificial Intelligencein the New Millenium, eds. Lakemeyer & Nebel, published by MorganKaufmann, 2002, which is incorporated herein by reference). The mappingalgorithm can include a statistical framework for simultaneously solvingthe mapping problem and the problem of localizing the lumen travelingdevice relative to the growing map using Kalman filters to estimate themap and the device location. The resulting map describes the location oflandmarks or significant features in the environment. Additionalinformation regarding mapping is described in Thrun, AI Magazine, 2000,21:93-109; Pfister et al., “Weighted line fitting algorithms for mobilerobot map building and efficient data representation,” Proceedings ofthe 2003 IEEE International Conference on Robotics and Automation,Taipei, Taiwan, Sep. 14-19, 2003; Thrun et al., “A real-time algorithmfor mobile robot mapping with applications to multi-robot and 3Dmapping,” Proceedings of the 2000 IEEE International Conference onRobotics and Automation, San Francisco, Calif., April 2000, each ofwhich is incorporated herein by reference. See also Filliat, D. andMeyer, J.-A., “Map-based navigation in mobile robots I. A review oflocalization strategies,” Cognitive Systems Research, Vol. 4, Issue 4,December 2003, pages 243-282, Elsevier B. V. and Meyer, J.-A. andFilliat, D., “Map-based navigation in mobile robots II. A review ofmap-learning and path-planning strategies,” Cognitive Systems Research,Vol. 4, Issue 4, December 2003, pages 283-317, Elsevier B. V., each ofwhich is incorporated herein by reference.

Other maps and mapping techniques may be used instead of, or the mappingtechniques described above. For example, a conformal map can be used inembodiments where it is desired to preserve information regarding anglesor areas of mapped regions, for purposes of visualization of surface.(see, e.g., Zhu, L., Haker, S., and Tannenbaum, A., “Flattening Maps forthe Visualization of Multibranched Vessels,” IEEE Transactions onMedical Imaging, Vol. 24, No. 2, pp. 191-198, February 2005, which isincorporated herein by reference).

In response to sensing a local parameter value, the lumen travelingdevice, and in particular an active portion of the lumen travelingdevice, can be instructed by the response control circuitry to performone or more actions. Examples of performing an action include but arenot limited to releasing a material, releasing a device or structure,releasing an energy, collecting a sample, collecting a device orstructure, attaching a structure to a wall of the body tube tree,delivering a material or structure to a receiving portion of a man-madedevice, receiving a material or structure from a delivery portion of aman-made device, receiving a signal from a remote source, receivingpower from a remote source, transmitting a signal to a remote location,performing a surgical step or procedure, removing tissue from at least aportion of the body tube tree, removing specific components of at leasta portion of a fluid from a body tube tree, exposing a catalyst,generating a localized electric field, generating a localized magneticfield, producing heat, causing cooling, emitting electromagneticradiation, emitting acoustic energy, applying pressure to at least aportion of the body tube tree, modulating the flow of a fluid through atleast a portion of the body tube tree, sensing a second local parametervalue, stopping performance of an action if the local parameter value iswithin a specified range, and initiating performance of an action if thelocal parameter value is within a specified range. Examples ofperforming an action are shown in FIGS. 15-19.

As shown in FIG. 15, the step of performing an action with the activeportion of the lumen traveling device (at step 1500) can includetransmitting a signal to a remote location (at 1502), or releasing amaterial (at step 1504), which can be, for example, at least one of atleast one of adhesive, a filler, a polymer, a hydrogel, an antibiotic,an antibody, an antiviral, a pharmaceutical compound, a nutrient, ahormone, a growth factor, a catalyst, a drug, a therapeutic compound, achemical, a biomaterial, a biological label, an enzyme, a protein, anucleic acid, an oligonucleotide, a polynucleotide, a polypeptide, agenetic material, a cell, a fraction of a cell, a cell fragment, acomplex, a vaccine, a vitamin, a neurotransmitter, a neurotropic agent,a neuroactive material, a cytokine, a chemokine, a hormone, acell-signaling material, a pro-apoptotic agent, an anti-apoptotic agent,an immunological mediator, an anti-inflammatory agent, a salt, an ion,an electrolyte, an antioxidant, an imaging agent, a labeling agent, adiagnostic compound, a nanomaterial, an inhibitor, a lipid, an alcohol,a sterol, a steroid, a carbohydrate, a sugar, a gas, or a blocker (asindicated at step 1506). As indicated at 1505, performing an action withan active portion of the lumen traveling device can include delivering amaterial to a wall region of the body tube tree. This can includedelivering a material to tissue in, on, or behind the wall of the bodytube tree, by injection, spraying, painting, printing, etc.

As shown in FIG. 16, performing an action with the active portion of thelumen traveling device 1500 can include collecting a material from thebody lumen (as shown in step 1602), which can include collecting asample from a fluid within the body lumen (as shown in step 1604), orcollecting a sample from a wall region of the body lumen (as shown instep 1606). The method can include collecting a sample from beyond thewall region of the body lumen, e.g., with the use of a needle topenetrate the body lumen wall. As further shown in FIG. 16, performingan action with the active portion of the lumen traveling device 1500 caninclude producing heating or causing cooling, as shown in steps 1608 and1616, respectively. Heating can be used in a variety of locations, for avariety of purposes, including but not limited to ablation orcauterization of tissue, or stimulation or inhibition of cellularfunctions. In one example, the method can include propelling the lumentraveling device through the body lumen to a location in the vicinity ofan atherosclerotic plaque, wherein performing an action with the activeportion can include producing heating to ablate the plaque, as shown instep 1610. In another example, performing an action with an activeportion includes heating to ablate a cancerous lesion, as shown in step1612. In another example, heating can be used in the male reproductivesystem to destroy gametes, as shown in step 1614.

Performing an action with the active portion can include securing thelumen traveling device into position within the body lumen as shown instep 1618, e.g., by using various positioning or lumen-wall-engagingstructures, examples of which have been described herein.

As shown in FIG. 17, performing an action with the active portion of thelumen traveling device 1500 can include emitting electromagneticradiation, as shown at step 1702. The performing an action can includeemitting ultraviolet, optical, infrared, microwave, or millimeter waveelectromagnetic radiation, as indicated at steps 1704, 1706, 1708, 1710,and 1712, respectively.

As shown in step 1802 of FIG. 18, performing an action with the activeportion of the lumen traveling device 1500 can include emitting acousticenergy, including, but not limited to, ultrasonic acoustic energy, asindicated in step 1804. As shown in FIG. 18, performing an action withthe active portion of the lumen traveling device can include applyingpressure to the body lumen (step 1806), by expansion of the activeportion, or by release of a gas or fluid. Performing an action with theactive portion of the lumen traveling device can include modulating theflow of fluid through at least a portion of the body lumen, as shown atstep 1808, for example by blocking the flow of fluid through at least aportion of the body lumen (step 1810), modifying the direction of flowof fluid through at least a portion of the body lumen (step 1812), ormodifying the amount of turbulent flow (step 1814). Modifying thedirection of flow of fluid can include directing flow, toward aparticular region and/or into a particular branch of a branching lumen,for example, with the use of various flow-directing structures asdisclosed herein. Modifying the direction of flow of fluid can alsoinclude reversing the direction of flow, which can be accomplished, forexample, by modifying the pressure within the lumen, as describedherein.

As shown in FIG. 19, performing an action with the active portion of thelumen traveling device 1500 can include at least partly removingspecific components from at least a portion of a fluid within the bodylumen, as shown at step 1902, or exposing a catalyst, as shown at step1904. Performing an action with the active portion can includegenerating a localized electric field, as shown at step 1906, generatinga localized magnetic field, as shown at step 1908, or removing tissuefrom or cutting at least a portion of the body lumen, as indicated atsteps 1910 and 1912, respectively. Performing an action with the activeportion can include releasing a man-made structure from the lumentraveling device, as shown at step 1914, and, in some embodiments,attaching the man-made structure to a wall of the body lumen, as shownat step 1916. As further shown in FIG. 19, performing an action with theactive portion of the lumen travel device at step 1500 can includedelivering a material or structure to a receiving portion of a man-madedevice, as shown at 1918, receiving a material or structure from adelivery portion of a man-made device, as shown at 1920. Finally,performing an action can include one or more of transmitting power tothe lumen traveling device, as shown in step 1922, transmitting a signalto the lumen traveling device, as shown in step 1924, receiving a signalfrom a remote source with the lumen traveling device, as shown in step1926, or receiving power from a remote source with the lumen travelingdevice, as shown in step 1928. Performing an action can includetransmitting an encrypted signal to the lumen traveling device (1925) orreceiving an encrypted signal from a remote source (1927).

FIGS. 20A and 20B depict lumen traveling device 2000 moving through alumen of a body tube tree 2002, sensing one or more local parametervalue and performing an action with an active portion 2012. Lumentraveling device 2000 includes sensor 2006, response control circuitry2010, and active portion 2012. Lumen traveling device 2000 also includesmotion control circuitry 2014. As shown in FIG. 20A, sensor 2006 sensesa local parameter value—in this case, material 2008 on the wall 2004 ofthe lumen of a body tube tree 2002. Material 2008 may be, for example, aplaque on the wall of an artery or a cancerous lesion in a bronchialairway. Sensor 2006 may be an optical sensor, an imaging device, orvarious other types of sensors, a number of which have been describedherein. Upon detection of material 2008, active portion 2012 may beactivated, as shown in FIG. 20B. In this example, active portion 2012performs ablation of material 2008; for example, active portion 2012 maybe an optical device which generates light 2016 to perform, for example,laser ablation of a plaque or cancerous lesion, or it may be an acousticdevice for performing ultrasonic ablation of a plaque or cancerouslesion.

FIG. 22A illustrates a method 2200 of operating a lumen traveling devicein a lumen of a body tube tree including activating a propellingmechanism on the lumen traveling device to propel the lumen travelingdevice within a body tube tree at 2202, determining a time based on asignal from a timing device at 2204, and performing at least one actionwith an active portion of the lumen traveling device based at least inpart upon the determined time at 2206. Variants of method 2200 aredepicted in FIGS. 22B-22E.

A signal from a timing device can be used to determine a time. Thetiming device for determining a time can be located on the lumentraveling device, or, alternatively, the timing device for determining atime can be a timing device associated with a remote device; see, forexample FIGS. 7 and 8. Thus, as shown in FIG. 22B, method 2201 (avariant of method 2200) can include determining a time based on a signalfrom a timing device, wherein the timing device is a remote timingdevice (2210) or wherein the timing device is on a lumen travelingdevice (2212). The timing device can include an oscillator timing devicesuch as, for example, quartz crystal oscillator, ceramic oscillator, aMEMS based CMOS timing circuit, film bulk acoustic resonator (FBAR), andsurface acoustic-wave (SAW) timing devices (see, e.g., Nguyen, IEEETrans Ultrasonics Ferroelectrics Frequency Controls, 54:251-270, 2007;U.S. Pat. No. 7,365,614, each of which is incorporated herein byreference.) The timing device can be a time processor unit (TPU), asemi-autonomous microcontroller designed for timing control. The TPU canoperate simultaneously with an integrated central processing unit (CPU)and can schedule tasks, process microcode read only memory (ROM)instructions, access data shared with the CPU, and perform input andoutput (I/O) functions. See, e.g., U.S. Pat. No. 7,020,231 which isincorporated herein by reference. In an embodiment, the timing device isa MEMS based resettable timer as described in U.S. Pat. No. 7,398,734,which is incorporated herein by reference. In an embodiment, the lumentraveling device include a chip-based or microelectromechanical systems(MEMS) scale atomic clock such as those described by Knappe, “EmergingTopics: MEMS Atomic Clocks,” in Comprehensive Microsystems, Y.Gianchandani, O. Tabata, and H. Zappe, (eds.), Volume 3, pp. 571-612,2007, Elsevier, Netherlands; and by Kitching, “Time for a betterreceiver: Chip-scale atomic frequency references,” GPS World, November2007, pp. 52-57, each of which is incorporated herein by reference.

The lumen traveling device can be instructed to perform an action basedon a time determined or measured by a timing device. For example, inmethod 2201, the method can including determining an absolute timemeasure (2214) based on a signal from the timing device. The lumentraveling device can be instructed to perform an action at a particulartime (e.g. 2:00 p.m.), where the current time is tracked by a clock onthe lumen traveling device or external to the lumen traveling device. Itshould be understood that the term “absolute time measure,” as usedherein, refers to a time measurement that is absolute with regard to thelumen traveling device system (that is, it is not changeable by thelumen traveling device system or determined relative to a lumentraveling device-specific event or events), which may, however, bedetermined relative to external world events or time measurements(including but not limited to local time of day, solar time, universaltime (UTC or UT1), terrestrial time (TT), international atomic time(TAI), etc.). In an embodiment, the lumen traveling device can beinstructed to perform an action at a particular ‘count’ on acontinuously running timer device on or external to the lumen travelingdevice, where the timer device is incremented at regular, knownintervals.

Alternatively, the method may include determining a relative timemeasure (2222). The relative time measure can be determined relative toan event (2224) or relative to a time of day (2226). The relative timedetermined by the timing device can be relative to an action or eventperformed by or occurring in relation to the lumen traveling device,including for example, and without limitation, arriving at a branchpoint, sensing a local parameter value, receiving a position indicatorsignal, traveling a specified distance, reaching a specific location inthe body tube tree based on a map of at least a portion of a body tubetree, performing an action, or any combination thereof. The relativetime measure can be set or reset, for example, when the lumen travelingdevice arrives and senses a branch point in the body tube tree. In anembodiment, the relative time can be set or reset by a remote signal,e.g. from a remote timing device. In an embodiment, the timing devicecan be external to the lumen traveling device, relaying specificinstructions at specific times to the lumen traveling device through atransmitter. In an embodiment, the lumen traveling device is instructedto perform an action based on timing relative to one or more timefiducial. The method can include setting a time fiducial (2216). Thetime fiducial can be set at or relative to the time at which the lumentraveling device is introduced into the subject. Alternatively, the timefiducial can be set at or relative to the time of an event, e.g.,arriving at a branch point, sensing a local parameter value, receiving aposition indicator signal, reaching a specific location in the body tubetree, or performing an action. As shown at 2218, the lumen travelingdevice can be instructed to perform an action at a determined time thatis less than the time fiducial (for example a lumen traveling device canbe instructed to travel while less than an hour has passed sinceintroduction of the lumen traveling device into the a subject's body).As shown at 2219, the lumen traveling device can be instructed toperform an action when the determined time is equal to the time fiducial(for example, a lumen traveling device can be instructed to release abolus of a drug when the determined time is exactly 3:30 p.m.). Inanother example, as shown at 2220, a lumen traveling device can beinstructed to perform an action at a determined time that is greaterthan the time fiducial (for example, the lumen traveling device can beinstructed to begin gathering data regarding blood chemistry 30 minutesafter delivery of a drug). The determined time can be a relative timemeasure, or it can be determined relative to an event or relative to atime of day. Similarly, the time fiducial can be set relative to anevent (as in the first example) or relative to an absolute time measure(as in the second example).

Referring again to FIG. 22B, in an embodiment, a method of operating alumen traveling device with a lumen traveling device control system caninclude activating a propelling mechanism on the lumen traveling deviceto propel the lumen traveling device within a body tube tree (2202);determining a time based on a signal from a timing device (2204);performing at least one action with the lumen traveling device based atleast in part upon the determined time (2206). In further options shownin 2208, the method can include detecting an arrival of the lumentraveling device at a branch point in the body tube tree with at leastone arrival sensor on the lumen traveling device, the branch pointincluding at least two branch channels (2228); selecting one of the atleast two branch channels (2230); and directing the lumen travelingdevice into the selected branch channel (2232). The method can includedetermining the time based on a signal from a remote timing device, orbased on a signal from a timing device located on the lumen travelingdevice. The method can include setting a time fiducial (2216); forexample, the time fiducial can be set relative to detection of anarrival of the lumen traveling device at the branch point. In anembodiment, an action can be performed while the determined time is lessthan the time fiducial (for example while less than some amount of timepassed since reaching the branch point). Alternatively, the action canbe performed when the determined time is equal to the time fiducial, orwhile the determined time is greater than the time fiducial. Thisapproach can be used to ensure that the action is taken either when thelumen traveling device is close to the branch point (as in the firstexample) or when it has travelled away from the branch point for someminimum amount of time (as in the second and third examples).

Method 2201 can include various additional steps, as represented bydashed box 2208 in FIG. 22B. Additional steps can include, for example,one or more of detecting an arrival of the lumen traveling device at abranch point in the body tube tree with at least one arrival sensor onthe lumen traveling device, the branch point including at least twobranch channels (2228), selecting one of the at least two branchchannels (2230), directing the lumen traveling device into the selectedbranch channel (2232) and/or storing information regarding the selectedbranch channel (2234), sensing a signal representative of a dimension ofa portion of the body tube tree toward which the lumen traveling deviceis traveling (2236), and reversing the direction of travel of the lumentraveling device if the signal representative of the dimension of theportion of the body tube tree indicates that the dimension of theportion of the body tube tree is less than a specified dimension (2238).Other examples of additional steps are shown in FIG. 22C. For example,the additional steps 2208 can include generating a map of at least aportion of the body tube tree 2240), which can include generating atopological map (2241), generating a metric map (2242), or generating aconformal map (2277), reading map data from a data storage location onthe lumen traveling device (2243), or sensing at least one positionindicator signal (see also 1302, FIG. 13) (2244), and can furtherinclude storing information regarding the selected branch channelderived from the at least one position indicator signal (2245), storinga representation of the at least one position indicator signal on thelumen traveling device (2246), or generating a map of at least a portionof the body tube tree based on the at least one position indicatorsignal (2247). Sensing at least one position indicator signal caninclude sensing at least one position indicator signal from an inertialnavigation system on the lumen traveling device (2248), sensing at leastone radiological signal originating from a remote source (2249), (whichcan include sensing a plurality or radiological signals from a pluralityof remote sources (2250), and/or determining position information fromthe at least one position indicator signal by determining theattenuation of the plurality of radiological signals from the pluralityof remote sources at the lumen traveling device (2251)). Sensing atleast one position indicator signal can include sensing at least oneultrasonic signal originating from a remote source (2252), for examplesensing a plurality of ultrasonic signals from a plurality of remotesources, and wherein determining position information from the at leastone position indicator signal includes determining at least one of theattenuation or phase change of the plurality of ultrasonic signals fromthe plurality of remote sources (2253), sensing at least oneelectromagnetic signal originating from a remote source (2254), such asa signal from an RF beacon (2255) or GPS signal (2256), or sensing atleast one magnetic signal originating from a remote source (2257).

As shown in FIG. 22D, performing at least one action with an activeportion of the lumen traveling device based at least in part upon thedetermined time (2206) can include releasing a material (2260),delivering a material to a wall region of the body tube tree (2278),releasing a device or structure (2261), releasing energy (2262),collecting a sample (2263), sensing at least one parameter valuerepresentative of an analyte (2264) (for example, sensing at least oneparameter value representative of glucose or lipids at a specific timerelative to a meal (2265), sensing at least one parameter valuerepresentative of an analyte at a specific time relative to release of adrug (2266), sensing at least one parameter value representative of ananalyte at a specific time relative to the occurrence of a physiologicalresponse (2267), collecting a device or structure (2268), attaching astructure to a wall of the body tube tree (2269), delivering a materialor structure to a receiving portion of a man-made device (2270),receiving a material or structure from a delivery portion of a man-madedevice (2271), receiving a signal from a remote source (2272), which maybe an encrypted signal, as shown at 1927 in FIG. 19, receiving powerfrom a remote source (2273), transmitting a signal to a remote location(2274), which may be an encrypted signal, as shown at 1925 in FIG. 19,performing a surgical step or procedure (2275), or removing specificcomponents from at least a portion of a fluid within the body tube tree(2276).

As further shown in FIG. 22E, the lumen traveling device can beinstructed to perform various actions based at least in part on adetermined time, including exposing a catalyst (2280), generating alocalized electrical field (2281), generating a localized magnetic field(2282), producing heat (2283), causing cooling (2284), emittingelectromagnetic radiation (2285), emitting acoustic energy (2286),applying pressure to a least a portion of the body tube tree (2287),modulating the flow of fluid through at least a portion of the body tubetree (2288), and/or sensing a second local parameter value (2289). In anembodiment, the lumen traveling device is instructed to perform anaction based at least in part upon the determined time and at least inpart upon receipt of an instruction from a remote device (2290).

The method can include communicating information with at least oneremote device (2291), which may include, for example, communicating animage, communicating a sensed parameter value, communicating a measuredparameter value, communicating a derived parameter value, communicatingdevice status information, or reporting an action (2292).

The lumen traveling device can be instructed to perform an action basedin part on a time if how or whether the action is performed is afunction of both time and some additional parameter value orinformation; performance of the action can depend upon a time, asdiscussed herein above, and also upon the value of a sensed parametervalue, an instruction from a user, etc. The additional parameter valueor information may be used to determine whether or not the action willbe performed (thus serving a gating or override function), or it maydetermine the nature or magnitude of the action (e.g., amplitude orduration of an electrical stimulus, quantity of drug released, etc.).

The lumen traveling device can be instructed to perform an action basedat least in part upon the determined time, over one or more timeinterval, as shown at 2293. In an embodiment, the lumen traveling devicecan be instructed to perform an action continuously over a specifiedtime interval (2294). In an embodiment, the lumen traveling device canbe instructed to periodically perform an action (2295). For example, thelumen traveling device can be instructed to capture an image of thelumen of a body tube tree every second over a determined period of timeas the lumen traveling device travels through the lumen. As anotherexample, the lumen traveling device can be instructed to sense aparameter periodically over at least one time interval (2296). Themethod can include sensing a parameter such as a chemical analyte (e.g.,pH) or physical parameter (e.g., lumen diameter) every second over adetermined time interval. As a further example, the lumen travelingdevice can be instructed to receive a position indicator signalperiodically over at least one time interval (2297), for example everysecond over a determined period of time to locate the position of thelumen traveling device in a body tube tree. In an embodiment, theinstructions can include placing a chemical or physical marker or labelas landmarks or indicators of the path of travel of the lumen travelingdevice. In the above example, the lumen traveling device performs anaction at uniform intervals (i.e., once every second). In someembodiments, the lumen traveling device may be instructed to perform anaction intermittently at non-uniform intervals or at random intervals.

Methods 2200 and 2201, and other variants thereof, can be performed, forexample, with a device as depicted in and described in connection withFIGS. 1, 2, 7 and 8.

FIG. 21 illustrates a block diagram of a system 2100 that includes a setof instructions 2104 for operating a lumen traveling device. Anembodiment of system 2100 is provided using non-transitory machinereadable media 2102 including a set of instructions 2104 including oneor more instructions that cause the lumen traveling device controlsystem to activate a propelling mechanism on a lumen traveling device topropel the lumen traveling device within a body tube tree; one or moreinstructions that cause the lumen traveling device control system todetermine a time based on a signal from a timing device; and one or moreinstructions that cause the lumen traveling device control system todirect the active portion of the lumen traveling device to perform atleast one action based at least in part upon the determined time. Theactive portion of the lumen traveling device can be directed to performvarious actions, as described elsewhere herein, for example. The one ormore instructions can be, for example, computer executable and/orlogic-implemented instructions. In an embodiment, the non-transitorymachine readable media 2102 can include computer readable media 2106. Inan embodiment, the non-transitory machine readable media 2102 caninclude recordable-type media 2108. A system as depicted in FIG. 21 canbe used in implementation of the method of FIG. 22A, for example. Itwill be appreciated that while system 2100 is specifically shown toinclude instructions for performing method 2200 depicted in FIG. 21A,system 2100 can be modified to perform any of the variants of method2200 and 2201 as depicted in FIGS. 22A-22E.

FIGS. 23A-23D provide an illustrative example of a lumen travelingdevice 2300 moving through a lumen of a body tube tree 2302 andperiodically performing an action based at least in part upon adetermined time. In FIG. 23A, lumen traveling device 2300 moving througha lumen of a body tube tree 2302 includes control circuitry 2304; anactive portion 2306 for releasing a material 2308; and propellingmechanism 2310. Propelling mechanism 2310 is a flagella-like propellingmechanism used to move lumen traveling device 2300 through the lumen ofa body tube tree 2302 as shown in FIG. 23B. The control circuitry 2304of lumen traveling device 2300 is operationally connected to the activeportion 2306 and includes motion control circuitry, response controlcircuitry and a timing device. The timing device of control circuitry2304 periodically signals to the response control circuitry to activatean active portion 2306. Activation of active portion 2306 by the controlcircuitry 2304 results in release of material 2308 into the lumen of abody tube tree 2302. In this example, the material 2308 collects asdeposits 2314 at discrete locations on the lumen wall 2312 as shown inFIG. 23C. After a period of time determined by the timing device, theresponse control circuitry of the control circuitry 2304 again causesactivation of the active portion 2306 and release of material 2308. Aslumen traveling device 2300 moves through a lumen of a body tube tree2302, deposits 2314 of material 2308 are left by the lumen travelingdevice 2300 at periodic intervals on the lumen wall 2312 as shown inFIG. 23D.

The timing device can be used to determine an elapsed time between twoevents or actions, e.g., detection of a branch point, detection ofspecified value(s) of one or more sensed local parameter value(s),receipt of position indicator signals, or combinations thereof.Information regarding elapsed time can be combined with the speed oftravel of the lumen traveling device to determined distance traveled.Conversely, information regarding time can be combined with distancetraveled by the lumen traveling device to determine the speed of thelumen traveling device. Information regarding absolute and relative timemeasures is stored in one or more data storage locations of the lumentraveling device and/or in one or more remote devices. The storedinformation regarding time in combination with other measuredparameters, e.g., position indicator signals, local parameter values, orproperties of branches, can be used to generate a map of a body tubetree.

FIG. 25A shows a method 2500 of operating a lumen traveling device in alumen of a body tube tree including identifying at least two possibledirections of travel of a lumen traveling device through a body tubetree, the body tube tree including a plurality of branched,interconnected channels, the at least two possible directions of travelcorresponding to at least two of the branched, interconnected channelsat 2502; receiving information related to whether or not at least one ofat least two possible directions of travel of the lumen traveling devicethrough the body tube tree has previously been traveled by the lumentraveling device at 2504; selecting a direction of travel from the atleast two possible directions of travel based at least in part on theinformation related to whether or not at least one of at least twopossible directions of travel of the lumen traveling device through thebody tube tree has previously been traveled by the lumen travelingdevice at 2506; and directing at least one of a steering mechanism and apropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree in the selecteddirection of travel at 2508. Method 2500 can include various additionalsteps at 2510, as will be discussed herein. In an embodiment, the stepsof method 2500 are performed by the lumen traveling device. In anembodiment, a portion of the steps of method 2500 are performed by thelumen traveling device and a portion of the steps of method 2500 areperformed at least in part by a remote device. The steps outlined inFIG. 25A can be performed using systems as described elsewhere herein.

As shown in FIG. 25B, directing at least one of a steering mechanism anda propelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree in the selecteddirection of travel (2508) can be performed under the control of motioncontrol circuitry located on-board the lumen traveling device (2509),under the control of motion control circuitry located in part on-boardthe lumen traveling device and in part on a remote device (2510), orunder the control of motion control circuitry located on a remote device(2511). The method can include directing at least one of the steeringmechanism and the propelling mechanism on the lumen traveling device tocause the lumen traveling device to move through the body tube tree inthe selected direction of travel for a pre-determined distance (2512),directing at least one of the steering mechanism and the propellingmechanism on the lumen traveling device to cause the lumen travelingdevice to move through the body tube tree in the selected direction oftravel for a pre-determined duration (2513), directing at least one ofthe steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to move through thebody tube tree in the selected direction of travel until a stopinstruction is received from a remote device (2514), generating aninstruction to turn the lumen traveling device (2515), directing atleast one of the steering mechanism and the propelling mechanism on thelumen traveling device to cause the lumen traveling device to continuemoving in a current direction of travel (2516), directing at least oneof the steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to continue movingin a current direction of travel until a branch point is reached (2517),and directing at least one of the steering mechanism and the propellingmechanism on the lumen traveling device to cause the lumen travelingdevice to reverse its direction of travel (2518).

Arrival of the lumen traveling device at a decision point foridentifying at least two possible directions of travel, e.g., a branchpoint, in the body tube tree can be identified by one or more arrivalsensors as described elsewhere herein. The lumen traveling device isconfigured to receive additional information related to whether or notat least one of at least two possible directions of travel at the branchpoint has previously been traveled by the lumen traveling device.Receiving information related to whether or not at least one of at leasttwo possible directions of travel of the lumen traveling device throughthe body tube tree has previously been traveled by the lumen travelingdevice can include information regarding current direction of travel ofthe lumen traveling device, the current location of the lumen travelingdevice, and the position of the lumen traveling device relative to a mapof the body tube tree. The current direction of travel and location ofthe lumen traveling device can be determined based on one or moreposition indicator signals. The position indicator signals can be usedto place the lumen traveling device on a previously generated portion ofthe map of a body tube tree or to aide in generating a map of unmappedportions of the body tube tree. As the lumen traveling device travelsthrough the body tube tree, information regarding its path of travelrelative to the map is collected and stored in the data storage locationof the lumen traveling device or in a remote device. The currentdirection of travel and location of the lumen traveling device on themap is further compared with information gathered previously regardingpositioning of the lumen traveling device on the map to determine if thelumen traveling device has taken this path in the past and, if so, whenand/or how often. Method 2501 shown in FIG. 25C is a variant of method2500 shown in FIG. 25A. In an embodiment, the information relating to adirection previously traveled is received from a portion of the lumentraveling device (2521). In an embodiment, the information relating to adirection previously traveled is received from a remote device (2522).The information received can include, but is not limited to, one or moreof the direction of travel of the lumen traveling device (2523), thecurrent position of the lumen traveling device (2524), and receivinginformation regarding the presence or absence of a marker or labelindicating whether or not at least one of the at least two possibledirections of travel has previously been traveled by the lumen travelingdevice (2525), for example the presence or absence of a chemical markeror label (2526) or a physical marker or label (2527).

Information related to whether or not at least one of at least twopossible directions of travel of the lumen traveling device through thebody tube tree has previously been traveled by the lumen travelingdevice can be information regarding one or more landmarks sensed in thelumen of a body tube tree. The one or more landmarks can be inherentchemical or physical markers or labels present at specific locations inthe lumen of a body tube tree. An inherent chemical marker or label caninclude but is not limited to a specific protein, a nucleic acid, anoligonucleotide, a polynucleotide, lipid, carbohydrate, a sugar,chemical compound, and the like, expressed on the surface of or excretedfrom specific cells at specific locations in the lumen of the body tubetree. An inherent physical landmark can include but is not limited to abranch point, a valve, a growth (e.g., polyp, plaque, fibroid, tumor), adiscoloration, a lumen occlusion or expansion, an aneurysm or othermeasurable local alteration in the physical properties of a lumen. Theinherent chemical or physical landmark can be represented by one or moreof a variety of local parameters previously described herein.Alternatively, the one or more landmarks can be chemical or physicalmarkers or labels previously placed in the lumen by an active portion ofthe lumen traveling device while traveling though the body tube tree.

FIGS. 26A-26C depict lumen traveling device 2600 moving through a lumenof a body tube tree 2602 and selecting a direction of travel based onsensing one or more markers or labels. In this example, lumen travelingdevice 2600 includes one or more wall engaging elements 2604 for use inpropelling lumen traveling device 2600 along the lumen wall 2606 of alumen of a body tube tree 2602. The lumen traveling device 2600 furtherincludes emitter/sensor system 2608, which emits electromagnetic energy2610. In this example, a first branch channel 2614 has been previouslymarked or labeled with a chemical or physical marker or label, which inthis example is fluorescent tag 2612, while a second branch channel 2616lacks a chemical or physical marker or label. In FIG. 26B, lumentraveling device 2600 reaches a branch point 2618 and must select adirection of travel. Emitter/sensor system 2608 of lumen travelingdevice 2600 senses electromagnetic energy 2620 generated by fluorescenttag 2612 in response to emitted electromagnetic energy 2610 of FIG. 26A.Electromagnetic energy 2620 is indicative of the presence of fluorescenttag 2612 in first branch channel 2614 and the lack thereof in secondbranch channel 2616. In FIG. 26C, lumen traveling device 2600 isinstructed to move into the second branch channel 2616, a branch channelnot previously traveled by lumen traveling device 2600.

Information related to whether or not a direction of travel has beenpreviously traveled by the lumen traveling device can be based onsensing one or more chemical marker or label previously placed in thelumen by an active portion of the lumen traveling device, as illustratedin FIG. 23. The chemical marker or label can be one or more of adetectable biomolecule including but not limited to a protein, a nucleicacid, an oligonucleotide, a polynucleotide, a peptide, an antibody, apolysaccharide, an oligosaccharide, a carbohydrate, a sugar, a lectin,an oligonucleotide, an aptamer, and the like. The chemical marker orlabel can be periodically released from an active portion of the lumentraveling device and configured to bind to or associate with the lumenwall of the body tube tree, as illustrated in FIG. 23. For example, anantibody can be designed to specifically bind an antigen expressed onthe surface of the lumen wall. In some instances, the chemical marker orlabel can be further modified with a physical marker or label, e.g., afluorescent label, that can be detected using a physical sensor, e.g., aCCD imaging device in response to excitation by electromagnetic energysource.

In an embodiment, information related to whether or not a direction oftravel has been previously traveled by the lumen traveling device can bebased on sensing one or more physical marker or label previously placedin the lumen by an active portion of the lumen traveling device. Thephysical marker or label can be one or more of a light emitting marker,a radioactive marker, magnetic marker, a visible marker, or aradiofrequency identification (RFID) tag. The physical marker or labelcan be a light emitting marker or label that is either intrinsicallylight emitting or that reflects light or emits light (e.g., byfluorescence) in response to excitation from an electromagnetic energysource. An example of a light emitting marker or label includes avariety of quantum dots or semiconductor nanocrystals that fluoresce atvarious wavelengths in response to excitation energy (see, e.g., Jaiswalet al., Nature Biotech., 2003, 21:47-51, which is incorporated herein byreference). Examples of other fluorescing dyes for use with biologicalsamples include but are not limited to fluorescein (FITC), indocyaninegreen (ICG) and rhodamine B, red and near infrared emitting fluorophores(600-1200 nm) including cyanine dyes such as Cy5, Cy5.5, and Cy7(Amersham Biosciences, Piscataway, N.J., USA) and/or a variety of AlexaFluor dyes such as Alexa Fluor 633, Alexa Fluor 635, Alexa Fluor 647,Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700 and Alexa Fluor 750(Molecular Probes—Invitrogen, Carlsbad, Calif., USA; see, e.g., U.S.Pat. App. No. 2005/0171434 A1, which is incorporated herein byreference). Additional fluorophores include IRDye800, IRDye700, andIRDye680 (LI-COR, Lincoln, Nebr., USA), NIR-1 and 1C5-OSu (Dojindo,Kumamoto, Japan), La Jolla Blue (Diatron, Miami, Fla., USA), FAR-Blue,FAR-Green One, and FAR-Green Two (Innosense, Giacosa, Italy), ADS 790-NSand ADS 821-NS (American Dye Source, Montreal, CA), NIAD-4 (ICxTechnologies, Arlington, Va.). Other fluorescing agents includeBODIPY-FL, europium, green, yellow and red fluorescent proteins,luciferase. Alternatively, the light emitting marker or label can be afluorescently labeled microsphere. Examples of fluorescently labeledmicrospheres ranging in diameter from 20 nanometers to 10 micrometersare available from commercial sources (e.g., Fluor Spheres® FluorescentMicrospheres, Invitrogen, Carlsbad, Calif.).

The physical marker or label can be one or more radioactive marker orlabel. The radioactive marker or label can include one or moreradioisotope commonly used in nuclear medicine, examples of whichinclude iodine-131, cobalt-60, cesium-137, technetium-99 m, carbon-11,nitrogen-13, oxygen-15, and fluorine-18. Other medical radioisotopesinclude but are not limited to, americium-241, arsenic-74, gold-198,boron-11, carbon-14, calcium-48, cerium-141, cobalt-55, cobalt-57,chromium-51, cesium-130, cesium-131, copper-61, copper-62, copper-64,copper-67, dysprosium-165, europium-155, gallium-67, gallium-68,gadolinium-153, germanium-68, hydrogen-3, iodine-122, iodine-123,iodine-124, iodine-125, iodine-132, indium-111, indium-115m,Iridium-191m, krypton-81m, manganese-51, manganese-52, Nb-95,osmium-194, phosphorous-32, phosphorous-33, lead-203, lead-82,ruthenium-97, ruthenium-103, sulfur-35, scandium-46, selenium-72,selenium-75, strontium-85, tantalum-178, tantalum-182, terbium-149,thallium-201, xenon-127, xenon-133.

The physical marker or label can be a magnetic marker or label such as,for example, magnetic beads, particles or carbon nanotubes. Magneticparticles and beads of various sub-millimeter size are available fromcommercial sources (from, e.g., Seradyn-Thermo Scientific, Indianapolis,Ind.; Dynal-Invitrogen, Carlsbad, Calif.). Carbon nanotubes with variousfunctionalities can be synthesized de novo (see, e.g. Bianco et al.,“Carbon nanotube-based vectors for delivering immunotherapeutics anddrugs,” in Nanomaterials for Medical Diagnosis and Therapy, pp. 85-142,Nanotechnologies for the Live Sciences, Vol. 10, Edited by Kumar,WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007, which is incorporatedherein by reference) or obtained from commercial sources (from, e.g.,Nanolab, Newton, Mass.; Swan Chemical Inc., Lyndhurst, N.J.).

The physical marker or label can be a visual marker or label such as,for example, an ink or dye visible with ultraviolet, visible, nearinfrared, or infrared electromagnetic energy emitted by the lumentraveling device. Examples of vital dyes used to stain cells include butare not limited to acridin orange (stains DNA and RNA), DiOC(3,3′-dihexyloxacarbocyanine iodide; stains endoplasmic reticulum),rhodamine 123 (stains mitochondria), Nile red (stains lipid vesicles),DAPI (4′,6-diamidino-2-phenylindole; stains DNA), Hoechst 33342 (stainsDNA). Calcein AM and carboxyfluorescein diacetate are examples ofmembrane permeable dyes that are converted into membrane-impermeabledyes by cellular esterases, thereby trapping them inside live cells.

The physical marker or label can be one or more radiofrequencyidentification tags, sub-millimeter versions of which have beendescribed (see, Hornyak, Scientific American Magazine, February 2008,pp. 68-71, which is incorporated herein by reference). Alternatively,the physical marker or label can be one or more bokodes, millimetersized visual tags that can be captured with a camera as described byMohan et al., “Bokode: Imperceptible visual tags for camera basedinteraction from a distance” ACM Transactions on Graphics (Proceedingsof SIGGRAPH 2009, Aug. 3-7, 2009, New Orleans, which is incorporatedherein by reference).

The chemical or physical marker or label is configured for attachment toor insertion into one or more cells and/or components of the basallamina lining the lumen of a body tube tree. Examples of cells liningthe lumen of body tube tree include but are not limited to endothelialcells (e.g., cells lining the vasculature) and epithelial cells (e.g.,cells lining the respiratory system including the mouth and nose, thedigestive tract including the anus, the urogenital tract, and the glandsof the digestive tract, prostate, and breast). In an embodiment, thechemical or physical marker or label can be directly applied to thesurface of the lumen by some means. For example, cell membranes can bereadily labeled with a number of fluorescent lipophilic dyes, examplesof which include DiI(1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate),DiO (3,3′-dioctadecyl-oxacarbocyanine perchlorate) and DiA4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide.

In an embodiment, the physical marker or label is modified with abinding moiety to enable interaction of the chemical or physical markeror label with the wall of the lumen. For example, a physical marker orlabel, e.g., a fluorescent dye, a radioisotope, or a magnetic bead, canbe linked to a binding moiety that selectively binds to the surface of acell and/or a component of the basal lamina lining the lumen of a bodytube tree. Examples of binding moieties include but are not limited toantibodies, aptamers, receptor binding ligands, peptide ligands. Afurther example of a binding moiety for linking a chemical or physicalmarker or label to the lumen is an antibody, aptamer or other bindingmoiety that selectively binds to a protein constitutively expressed onthe surface of endothelial or epithelial cells, specific examples ofwhich include intercellular adhesion molecule-1 (ICAM1) and epithelialcell adhesion molecule (EpCAM), respectively.

The chemical or physical marker or label can be conjugated to thebinding moiety using one or more of a cross linking agent. In general,any of a number of cross linking agents can be used to conjugate anappropriately derivatized chemical or physical marker or label to anappropriately derivatized binding moiety. Examples of cross linkingagents include, but are not limited to, primary amine/primary aminelinkers such as DMS (dimethyl suberimidate), DMP (dimethylpimelimidate), DSS (disuccinimidyl suberate), DST (disuccinimidyltartate), Sulfo DST (sulfodisuccinimidyl tartate), DSP(dithiobis(succinimidyl propionate) and sulfhydryl/sulfhydryl linkerssuch as DPDPB (1,4-di-(3′-[2′ pyridyldithio]-propionamido) butane);primary amine/sulfhydryl linkers such as MBS(m-maleimidobenzoyl-N-hydroxysuccinimide ester), Sulfo MBS(m-maleimidobenzoyl-N-hydroxysulfosuccinimide), Sulfo GMBS(N-γ-maleimidobutyryloxysulfosuccinimide ester),EMCS(N-(epsilon-maleimidocaproyloxy) succinimide ester), SulfoEMCS(N-(epsilon-maleimidocaproyloxy) sulfo succinimide), SMCC(succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate), SMPB(succinimidyl 4-(rho-maleimidophenyl) butyrate), Sulfo SIAB(N-sulfosuccinimidyl(4-iodoacetyl)aminobenzoate),cyclohexane-1-carboxylate), and MAL-PEG-NHS (maleimide PEGN-hydroxysuccinimide ester); sulfhydryl/hydroxyl linkers such as PMPI(N-rho-maleimidophenyl) isocyanate; sulfhydryl/carbohydrate linkers suchas EMCH (N-(epsilon-maleimidocaproic acid) hydrazide); andamine/carboxyl linkers such as EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride).

An antibody for use as a chemical or physical marker or label can beconjugated with one or more quantum dots via an amine-thiol linkageusing amine-derivatized, poly-ethylene glycol coated quantum dots andthe amine-thiol crosslinker SMCC with a commercially available kit(Qdot® Antibody Conjugation Kit, Invitrogen, Carlsbad, Calif.).Similarly, various methods are available for attaching quantum dots tothe DNA backbone of an aptamer such as, for example, covalent linkage ofamino-labeled DNA to carboxylated quantum dots and linkage ofbiotinylated DNA to streptavidin modified quantum dots. See, e.g., Cadyet al., Mol. Cell. Probes, 21:116-124, 2007, which is incorporatedherein by reference. For example, carboxy quantum dots (from, e.g.,Quantum Dot Corporation, Hayward, Calif., USA) can be attached to anaptamer through a C6 amino modifier placed on either the 5 prime or 3prime end of the aptamer sequence. Alternatively, streptavidin quantumdots (from, e.g., Quantum Dot Corporation, Hayward, Calif., USA) can beattached to an aptamer through a biotin attached to the 5-prime end ofthe aptamer sequence. Quantum dots, fluorescent dyes, and magneticparticles derivatized for cross-linking to antibodies, aptamers or otherbiomolecules are available from a number of commercial sources (from,e.g., Invitrogen, Carlsbad, Calif.; Seradyn-Thermo Scientific,Indianapolis, Ind.; Sigma-Aldrich, St. Louis, Mo.).

In an embodiment, a physical marker or label, e.g., radioactive orfluorescent, can be incorporated into the binding moiety at the time ofsynthesis. For example, radiolabeled nucleotides or radiolabeled aminoacids can be incorporated into an oligonucleotide aptamer or proteinantibody, respectively, during synthesis using standard methods. Asanother example, all or part of green fluorescent protein (GFP) derivedfrom Aequorea victoria jellyfish or yellow, red and blue fluorescingderivatives thereof, can be fused with a binding moiety (e.g., anantibody) designed to bind to or associate with the surface of thelumen. A number of expression constructs for generating recombinant GFPfusion proteins are available from commercial sources (from, e.g.,Invitrogen, Carlsbad, Calif.).

In an embodiment, the marker or label can be a DNA construct encoding afluorescent protein and inserted into one or more cells lining the lumenof a body tube tree. For example, baculovirus expression constructs,e.g., Cellular Lights™ and Organelle Lights™ (from Invitrogen, Carlsbad,Calif.), can be inserted into a cell and induced to express specificfluorescent proteins.

In an embodiment, the chemical or physical marker or label can beinserted into one or more cells lining the lumen of the body tube tree.The marker or label can be inserted by direct injection, diffusion,fusion, or other means. For example, the lumen traveling device caninclude an active portion that includes one or more microneedles fordirect injection of a chemical or physical marker or label into a cell.Alternatively, the lumen traveling device can include an active portionthat includes a material release structure for releasing one or morechemical or physical marker or label into the lumen of a body tube tree.The chemical or physical marker or label can be periodically placedalong the path of travel of the lumen traveling device by an activeportion of the lumen traveling device, as described, for example, inconnection with FIG. 23. The periodic placement can be based on distancetraveled by the lumen traveling device, e.g., every one millimeter. Theperiodic placement of the chemical or physical marker or label by anactive portion of the lumen traveling device can be completed based ontime between placements, e.g., every second. The periodic placement ofchemical or physical marker or labels in the lumen of the body tube treecan be used to inform selection of one of at least two possibledirections of travel.

The selected direction of travel of the lumen traveling device can beselected based on information regarding whether or not at least one ofat least two possible directions of travel have been previously traveledby the lumen traveling device. As shown in FIG. 25D, in an embodiment,the selected direction of travel can be a direction of travel notpreviously traveled by the lumen traveling device (2530). For example,the selected direction of travel may be the direction of travel devoidof chemical or physical markers or labels. In an embodiment, theselected direction of travel can be a direction of travel that is theleast frequently traveled by the lumen traveling device of the at leasttwo possible directions of travel (2531). In an embodiment, the selecteddirection of travel can be a direction of travel that is the mostfrequently traveled by the lumen traveling device of the at least twopossible directions of travel (2532). For example, comparison of thecurrent direction of travel of the lumen traveling device and thelocation of the lumen traveling device on a map of the body tube treecan be used to determined how frequently the lumen traveling device hastraveled in the possible directions of travel. In an embodiment, theselected direction of travel can be a direction of travel that is theleast recently traveled by the lumen traveling device of the at leasttwo directions of travel (2533). In an embodiment, the selecteddirection of travel can be a direction of travel that is the mostrecently traveled by the lumen traveling device of the at least twodirections of travel (2534). Information regarding the frequency oftravel in one of at least two possible directions of travel can bestored in and/or retrieved from one or more data storage locationassociated with the lumen traveling device and/or a remote device.Information regarding the frequency of travel in one of at least twopossible directions of travel is further correlated with a pre-existingmap or an evolving map of the body tube tree and used to inform theselection of the direction of travel of the lumen traveling device.Selecting a direction of travel can also include avoiding at least oneportion of the body tube tree having a dimension less than a specifiedminimum dimension (2535). Variants of the methods 2500 and 2501 caninclude additional steps 2510, which as shown in FIG. 25D, can includestoring a record of the selected direction of travel 2536. In anembodiment, the method can include directing an active portion of thelumen traveling device to mark or label the selected direction of travel(2537), directing an active portion of the lumen traveling device tomark or label the selected direction of travel by marking or labeling aselected body lumen with a chemical marker or label (2538). A chemicalmarker or label may be a biochemical marker or label, which can includea nucleic acid (2540) or protein (2541). In an embodiment, a chemicalmarker or label includes a radioactive marker or label (2542). In anembodiment, the method includes directing an active portion of the lumentraveling device to mark or label the selected direction of travel bymarking or labeling a selected body lumen with a physical marker orlabel (2543). A physical marker or label can include a magnetic markeror label (2544), optically detectable marker or label (2545),magnetically detectable marker or label (2546), or an electricallydetectable marker or label (2548).

Further additional steps 2510 are depicted in FIG. 25E, and includesensing a local parameter value with a parameter sensor on the lumentraveling device (2550), identifying a stop condition based at least inpart on the sensed local parameter value; and directing at least one ofthe steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to stop movement ofthe lumen traveling device through the body tube tree based at least inpart on the identified stop condition (2551), storing data representingthe sensed local parameter value in a memory location on the lumentraveling device (2552), transmitting data representing the sensed localparameter value from the lumen traveling device to a remote device(2553), storing motion control instructions for directing operation ofat least one of the steering mechanism and the propelling mechanism in amemory location on the lumen traveling device (2554), transmittingmotion control instructions for directing operation of at least one ofthe steering mechanism and the propelling mechanism on the lumentraveling device to a remote device (2555), receiving at least one ofinstructions or data from a remote device (2556), wherein the methodsteps are performed by the lumen traveling device (2557), and wherein aportion of the method steps are performed by the lumen traveling deviceand a portion of the method steps are performed at least in part by aremote device (2558).

Motion control instructions are generated to cause movement of the lumentraveling device in the selected direction of travel. The motion controlinstructions are configured to instruct the lumen traveling device to goright, to go left, to turn a certain number of degrees, to go up, to godown, to continue moving in the current direction, or to reverse. In anembodiment, the motion control instructions can for directing operationof at least one of the steering mechanism and the propelling mechanismon the lumen traveling device to cause the lumen traveling device tomove through the lumen of a body tube tree in the selected direction oftravel for a pre-determined distance, for a pre-determined time, oruntil a branch point is reached, or until a combination of suchdistance, time and location criteria are attained. An arrival of thelumen traveling device at a branch point is detected using one or morearrival sensors as described elsewhere herein. In an embodiment, themotion control instructions are stored in a data storage location on thelumen traveling device. In another embodiment, the motion controlinstructions can be transmitted from the lumen traveling device, to aremote device. In yet another embodiment, the motion controlinstructions are received at least in part from a remote device.

The motion control instruction can direct operation of at least one ofthe steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to move through abody tube tree in the selected direction of travel until a stopinstruction is received from a remote device. The stop instruction canbe based on elapsed time, calculated distance of travel, or actualimaging or sensing of the location of the lumen traveling device in thebody tube tree. For example, the stop instruction may be received afterthe lumen traveling device has traveled through the body tube tree for aspecific period of time following receipt of the motion controlinstruction. As a further example, the stop instruction may be receivedafter the lumen traveling device has reached a specific location. Anarrival of the lumen traveling device at a specific location can bedetermined based on the location of the lumen traveling device on a mapof the body tube tree.

An arrival of the lumen traveling device at a specific location can bedetermined by remote sensing using one or more medical imagingtechniques. For example, an external medical imaging technique can beused to monitor in real time the movement of the lumen traveling devicefrom outside the body and once the lumen traveling device has reached aspecific location, a remote signal can be sent to the lumen travelingdevice to stop movement. The lumen traveling device can be labeled orcan emit a signal (e.g., radiofrequency) while the body tube tree itselfcan be labeled with a contrast agent. As a further example, the lumentraveling device can be constructed from or coated with a radiopaquematerial and visualized relative to the vasculature using angiography orother imaging method.

The motion control instructions can direct operation of at least one ofthe steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to move through abody tube tree in the selected direction of travel until a stopinstruction is received based on sensing a local parameter value withone or more parameter sensors. Examples of sensors for sensing localparameter values have been described elsewhere herein. Informationregarding the sensed local parameter value is stored in a data storagelocation on the lumen traveling device. Alternatively, or in addition,data regarding the sensed local parameter value may be transmitted to aremote device.

FIG. 24 illustrates a block diagram of a system 2400 that includes a setof instructions 2404 for operating a lumen traveling device. Anembodiment of system 2400 is provided using non-transitory machinereadable media 2402 including a set of instructions 2404 including oneor more instructions that cause the lumen traveling device controlsystem to identify at least two possible directions of travel of a lumentraveling device through a body tube tree, the body tube tree includinga plurality of branched, interconnected channels, and the at least twopossible directions of travel corresponding to at least two of saidbranched, interconnected channels; one or more instructions that causethe lumen traveling device control system to receive information relatedto whether at least one of the at least two possible directions oftravel of the lumen traveling device through the body tube tree haspreviously been traveled by the lumen traveling device; one or moreinstructions that cause the lumen traveling device control system toselect a direction of travel from the at least two possible directionsof travel based at least in part on the information related to whetheror not at least one of the at least two possible directions of travel ofthe lumen traveling device through the body tube tree has previouslybeen traveled by the lumen traveling device; and one or moreinstructions that cause the lumen traveling device control system todirect at least one of a steering mechanism and a propelling mechanismon the lumen traveling device to cause the lumen traveling device tomove through the body tube tree in the selected direction of travel. Theone or more instructions can be, for example, computer executable and/orlogic implemented instructions. In an embodiment, the non-transitorymachine readable media 2402 includes computer readable media 2406. In anembodiment, the non-transitory machine readable media 2402 includesrecordable-type media 2408. A system as depicted in FIG. 24 can be usedin implementation of the method of FIG. 25A, for example. It will beappreciated that while system 2400 is specifically shown to includeinstructions for performing method 2500 depicted in FIG. 25A, system2400 can be modified to perform any of the variants of method 2500 and2501 as depicted in FIGS. 25A-25E.

A further method 2800 of operating a lumen traveling device in the lumenof a body tube tree of a subject is illustrated in FIG. 28A andcomprises identifying at least two possible directions of travel of alumen traveling device through a body tube tree, the body tube treeincluding a plurality of branched, interconnected channels, and the atleast two possible directions of travel corresponding to at least two ofthe branched, interconnected channels at 2802; receiving datarepresenting at least one parameter value sensed from at least one ofthe at least two possible directions of travel of the lumen travelingdevice through the body tube tree at 2804; selecting a direction oftravel from the at least two directions of travel based at least in parton the data representing at least one parameter value sensed from atleast one of the at least two possible directions of travel of the lumentraveling device through the body tube tree at 2806; and directing atleast one of the steering mechanism and the propelling mechanism on thelumen traveling device to cause the lumen traveling device to movethrough the body tube tree in the selected direction of travel at 2808.The steps outlined in FIG. 28 can be performed using systems asdescribed elsewhere herein.

FIG. 28B illustrates method 2801, which is a variant of method 2800depicted in FIG. 28A. Method 2801 includes steps 2802, 2804, 2806, and2808 as described in connection with FIG. 28A, as well as additionalsteps 2810, which in the embodiment shown in FIG. 28B include receivingat least one user input instruction from a medical care provider, theuser input instruction related to selecting a parameter type of the atleast one parameter sensed from the at least one of the at least twopossible directions of travel of the lumen traveling device through thebody tube tree (2820) and/or receiving at least one user inputinstruction from a medical care provider, the user input instructionrelated to selecting a parameter value range for the at least oneparameter value sensed from the at least one of the at least twopossible directions of travel of the lumen traveling device through thebody tube tree (2821).

FIG. 28C depicts variants of directing at least one of a steeringmechanism and a propelling mechanism on the lumen traveling device tocause the lumen traveling device to move through the body tube tree inthe selected direction of travel (2808), which can include directing atleast one of the steering mechanism and the propelling mechanism on thelumen traveling device to cause the lumen traveling device to movethrough the body tube tree in the selected direction of travel for apre-determined distance (2822), directing at least one of the steeringmechanism and the propelling mechanism on the lumen traveling device tocause the lumen traveling device to move through the body tube tree inthe selected direction of travel for a pre-determined duration (2823),directing at least one of the steering mechanism and the propellingmechanism on the lumen traveling device to cause the lumen travelingdevice to move through the body tube tree in the selected direction oftravel until an stop instruction is received from a remote device by thelumen traveling device (2824), directing at least one of the steeringmechanism and the propelling mechanism on the lumen traveling device tocause the lumen traveling device to turn (2825), directing at least oneof the steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to continue movingin a current direction of travel (2826), directing at least one of thesteering mechanism and the propelling mechanism on the lumen travelingdevice to cause the lumen traveling device to reverse its direction oftravel (2827), directing at least one of the steering mechanism and thepropelling mechanism on the lumen traveling device to cause movement ofthe lumen traveling device based on a previous movement direction(2828), directing at least one of the steering mechanism and thepropelling mechanism on the lumen traveling device to cause the lumentraveling device to move in a different direction the direction it waspreviously instructed to move (2829), directing at least one of thesteering mechanism and the propelling mechanism on the lumen travelingdevice to cause the lumen traveling device to move in the same directionit was previously directed to move (2830).

The lumen traveling device is configured to receive data representing atleast one parameter value sensed from at least one of at least twopossible directions of travel. The at least two possible directions oftravel can be at a branch point with two or more branches representingtwo or more possible directions of travel. Arrival of the lumentraveling device at a branch point in the body tube tree can be sensedby one or more arrival sensors. The at least two possible directions oftravel can also be in any direction of travel away from the currentlocation of the lumen traveling device, e.g., up, down, right, left,forward, backward, diagonal, etc. A direction of travel away from thecurrent location can be selected based on data regarding one or morelocal parameters of interest in the lumen of the body tube tree. Dataregarding one or more local parameters can be obtained from one or moresensors. The one or more sensors can be configured to measure at leastone parameter value, including, but not limited to, a temperature, apressure, a fluid flow, an optical absorption, optical emission,fluorescence, or phosphorescence, an index of refraction, an electricalresistivity, a density or sound speed, a pH, an osmolality, the presenceof an embolism, the presence (or absence) of an object (such as a bloodclot, a thrombus, an embolus, a plaque, a lipid, a kidney stone, a dustparticle, a pollen particle, a gas bubble, an aggregate, a cell, aspecific type of cell, a cellular component or fragment, a collection ofcells, a gamete, a pathogen, or a parasite), and/or the presence (orabsence) of a substance such as a biological marker, an antibody, anantigen, a peptide, a polypeptide, a protein, a complex, a signalingmaterial, a nucleic acid, an oligonucleotide, a polynucleotide, a cell(and, in some cases, a cell of a particular type, e.g. by methods usedin flow cytometry), a cellular component, an organelle, a gamete, apathogen, a lipid, a lipoprotein, an alcohol, an acid, an ion, animmunomodulator, a sterol, a steroid, a carbohydrate, a sugar, apolysaccharide, a glycoprotein, a metal, an electrolyte, a metabolite,an organic compound, an organophosphate, a drug, a therapeutic, a gas, apollutant, or a tag (e.g., chemical or physical marker or label), forexample. Specific examples of sensors include one or more of a pressuresensor, a flow sensor, a temperature sensor, an optical sensor, abiosensor, or a chemical sensor. The selection of a suitable sensor fora particular application or use site is considered to be within thecapability of a person having skill in the art. In some aspects, asensor can include signal processing or pre-processing capabilityintegrated therewith.

In an embodiment, the sensed parameter is electromagnetic energy emittedby the lumen traveling device. For example, the lumen traveling devicecan be configured to sense autofluorescence emitted from cells of thelumen wall, to differentiate between normal and diseased cells, and tomove in the direction of the diseased tissue based on the sensedautofluorescence parameter. The lumen traveling device can be configuredto sense autofluorescence emitted from lumen wall tissue that has beenilluminated with specific wavelengths of electromagnetic energy from,for example, one or more of a microscale light-emitting diode or quantumdot. Endogenous fluorophores associated with the lumen wall absorb theelectromagnetic energy delivered from the lumen traveling device andre-emit it as fluoresced light at a longer wavelength. Theautofluorescence can be sensed with one or more of a light or imagecapture device, e.g., CCD, CMOS, or other similar device. Tissueautofluorescence can originate from aromatic amino acids such astryptophan, tyrosine, and phenylalanine (excitation wavelengths of200-340 nm, emission wavelengths of 360-370, 455 nm), from reducedpyridine nucleotides such as nicotinamide adenine dinucleotide (NADH,excitation wavelength of 360 nm, emission wavelength of 460 nm), fromflavins and flavin nucleotides such as riboflavin and flavinmononucleotide (excitation wavelengths of 360 nm, 445-470 nm, emissionwavelengths of 440 nm, 520 nm), from structural proteins such ascollagen, and from lipopigments such as ceroid and lipofuscin. See,e.g., Chung et al., Current Surgery, 62:365-370, 2005, and Dacosta etal., J. Clin. Path., 58:766-774, 2005, each of which is incorporatedherein by reference. Differences in the properties of emittedautofluorescence can be used to distinguish between normal and cancerouscells in a variety of epithelial organ systems, including the cervix,colon, bladder, bronchus and oral mucosa (See, e.g., Breslin et al.,Ann. Surg. Oncol., 2004, 11:65-70; Weingandt et al., BJOG 2002,109:947-951; Chiyo et al., Lung Cancer, 2005, 48:307-313; Eker et al.,Gut, 1999, 44:511-518, each of which is incorporated herein byreference). For example, changes in autofluorescence emission (350 to700 nm) of premalignant or malignant lesions in the oral cavity relativeto normal tissue can be detected using excitation wavelengths of 337 nm,365 nm, and 410 nm (see, e.g., Gillenwater et al., Arch. Otolaryngol.Head Neck Surg., 1998, 124:1251-1258, which is incorporated herein byreference). Cervical intraepithelial neoplasia can be differentiatedfrom normal tissue by autofluorescence using an excitation wavelength of355 nm (see, e.g., Nordstrom et al., Lasers Surg. Med., 2001,29:118-127, which is incorporated herein by reference). Autofluorescencein combination with reflected light can be used to differentiate betweennormal, inflamed and pre-invasive lesions in the lung (see, e.g.,Gabrecht et al., Diagnostic Optical Spectroscopy in Biomedicine IV:Proc. SPIE-OSA Biomedical Optics, 2007, Vol. 6628, 66208C-1-8; U.S. Pat.No. 5,507,287, each of which is incorporated herein by reference).Autofluorescence associated with macrophages in a plaque can be used tocharacterize an atherosclerotic lesion as described by Marcu et al.,Atherosclerosis, 2005, 181:295-303, which is incorporated herein byreference. The accumulation of macrophages in the fibrous cap of anatherosclerotic plaque are indicative of inflammation as well asinstability of the plaque and can be detected by irradiation of thelumen wall with electromagnetic energy at a wavelength of 337 nm andsensing autofluorescence at specific maxima wavelengths of 395 nm and450 nm or over a range of wavelengths from 300-600 nm.

As shown in FIG. 28D, additional step 2810 can include receiving datarepresenting at least one parameter value sensed from at least one ofthe at least two possible directions of travel of the lumen travelingdevice through the body tube tree (2831), which may include receivingdata representing an analyte (2832), for example, receiving datarepresenting an analyte selected from the list consisting of a chemical,a biomaterial, an ion, an electrolyte, a biological marker, an antibody,a polypeptide, a protein, a nucleic acid, an oligonucleotide, apolynucleotide, a complex, a pathogen, a signaling material, a lipid, analcohol, a sterol, a steroid, a carbohydrate, a sugar, a drug, atherapeutic, a gas, a metabolite, a cytokine, a chemokine, a hormone, aninflammatory molecule, a cell, and a cell fragment (2833). Datarepresentative of an analyte can be data representative of the presenceor concentration of an analyte, for example.

In an embodiment, the sensed parameter can be one or more analytesreleased from a target location within a body tube tree. The targetlocation can be a tumor or localized site of inflammation from whichanalytes such as tumor markers and/or inflammatory mediators aresecreted. Examples of tumor markers found in blood include but are notlimited to prostate-specific antigen (PSA), cancer antigen 125 (CA 125),CA19-9 antigen, calcitonin, alpha-fetoprotein (AFP), human chorionicgonadotropin (HCG). Examples of inflammatory mediators include but arenot limited to cytokines, interferons, interleukins, chemokines,leukotrienes, prostaglandins, growth factors, soluble receptors, and thelike. Tumor markers and inflammatory mediators may also be found inexpired breath condensate. A number of analytes are detected in theexpired breath of cancer patients, examples of which include but are notlimited to volatile organic compounds (VOCs), interleukin 6 (IL-6), andendothelin-1 (see, e.g., Dweik & Amann, J. Breath Res., 2008, 030301 (3pp) and Phillips et al., Chest, 2003, 123:2115-2123, each of which isincorporated herein by reference). Analytes associated with inflammationof the lungs have also been detected in expired breath and include8-isoprostane and nitric oxide (see, e.g., Psathakis et al., Chest,2004, 125:1005-1011, which is incorporated herein by reference). Anumber of specific volatile organic compounds are elevated in theexpired breath of subjects with cancer, including but not limited tobutane, 3-methyl tridecane, 7-methyl tridecane, 4-methyl octane,3-methyl hexane, heptane, 2-methyl hexane, pentane, and 5-methyl decane.Exhaled analytes associated with various diseases and/or lesions of thelungs can include nitric oxide, other volatile gases (e.g. carbonmonoxide, ethan, pentane), and endogenous substances (e.g., inflammatorymediators, cytokines, oxidants) (see, e.g., Kharitonov et al., Am. J.Respir. Crit. Care Med., Vol. 163, pp. 1693-1722, 2001, which isincorporated herein by reference).

Information regarding a local parameter can be collected using one ormore of a sensing or information gathering devices or structures. Thelumen traveling device can include one or more sensors of the same ordifferent types including but not limited to, pressure sensors,temperature sensors, flow sensors, viscosity sensors, shear sensors(e.g., for measuring the effective shear modulus of the fluid at afrequency or strain-rate), pH sensors, chemical sensors for determiningthe presence or concentration of a chemical compound or species, opticalsensors, acoustic sensors, biosensors, electrical sensors, magneticsensors, clocks or timers. Examples of a variety of sensors that can beused in embodiments described herein are provided in U.S. Pat. Nos.5,522,394; 5,873,835; 6,053,873; 6,409,674; 6,111,520; 6,278,379;6,475,639; 6,802,811; and 6,855,115, and U.S. Patent Applications2005/0277839 and 2005/0149170, each of which is incorporated herein byreference. In some aspects, an imaging device (e.g., a CCD array) can beoperatively connected to the lumen traveling device. Informationregarding one or more local parameter sensed by the lumen travelingdevice while traveling through a body tube tree can be stored in one ormore data storage locations within the lumen traveling device or in oneor more remote devices. As shown in FIG. 28D, additional step 2810 caninclude receiving data representing a temperature (2834), receiving datarepresenting a pressure (2835), receiving data representing a fluid flow(2836), receiving data representing a structural parameter of at leastone of the plurality of branched interconnected channels (2837), forexample, receiving data representing a length, width, diameter,thickness, direction, orientation, structural configuration, branchingpattern, distance from a branch point, proximity to a valve, orproximity to a channel restriction of at least one of the plurality ofbranched interconnected channels (2838), receiving data representing anelectrical field (2839), receiving data representing a magnetic field(2840), receiving data representing an electromagnetic signal (2841),receiving data representing an acoustic signal (2842), receiving datarepresenting an optical signal (2843), receiving data from at least oneparameter sensor on the lumen traveling device (2844), receiving datafrom a remote device (2845), receiving data representing at least oneparameter value sensed from at least one of the at least two possibledirections of travel at least two different times, and wherein selectinga direction of travel from the at least two directions of travel basedat least in part on the data includes selecting the direction of travelbased on the value of a function of the at least one parameter at the atleast two different times (2846).

In an embodiment, a medical provider or other caregiver can input one ormore instructions that cause the lumen traveling device control systemto select a parameter type to be sensed by the lumen traveling device.The parameter type to be sensed can be selected based on data receivedfrom the lumen traveling device or from a remote device regarding acondition of the subject. For example, if diagnostic medical imagingindicates the presence of a tumor at a location within a body tube tree,the lumen traveling device can be instructed by the medical provider orother caregiver to seek out the tumor by sensing one or more parameters,e.g., tumor markers, associated with the tumor and to move in thedirection of the tumor. A medical provider or other caregiver canfurther input one or more instructions that cause the lumen travelingdevice control system to select a parameter value range. The selectionof one or more parameters to be sensed by the lumen traveling device canbe programmed into the lumen traveling device prior to insertion intothe body tube tree of a subject. Alternatively, the selection of one ormore parameters to be sensed can be sent wirelessly to a lumen travelingdevice already residing in the lumen of a body tube tree. For example, asignal can be transmitted from a remote device to a receiver on thelumen traveling device to instruct the lumen traveling device to utilize(receive information from) specific on-board sensors. The remote devicecan include a computer terminal or other device configured to interfacewith a medical provider or caregiver.

The direction of travel of the lumen traveling device can be selectedbased on one or more parameters sensed in the lumen of the body tubetree. The direction of travel can be selected such that the lumentraveling device will move along a gradient of one or more parameters,so that movement of the lumen traveling device along the gradient willmove the lumen traveling device toward or away from a location or regionof interest, e.g. a source of a chemical marker, a source or area ofhigh fluid flow, a larger or smaller channel dimension, etc. Motioncontrol instructions are generated to cause movement of the lumentraveling device in the selected direction of travel. The motion controlinstructions can direct movement of the lumen traveling device throughthe lumen of a body tube tree in the selected direction of travel for apre-determined distance and/or a pre-determined time. In a embodiment,the motion control instructions can direct the propelling mechanism andthe steering mechanism to cause movement of the lumen traveling devicethrough a body tube tree in the selected direction of travel until astop instruction is received from a remote device. The stop instructioncan be based on elapsed time, calculated distance of travel, or actualimaging or sensing of the lumen traveling device location in the bodytube tree. For example, the stop instruction may be received after thelumen traveling device has traveled through the body tube tree for aprescribed period of time since receipt of the motion controlinstruction. As a further example, the stop instruction may be receivedafter the lumen traveling device has reached a specific location.Alternatively, the motion control instruction can cause movement of thelumen traveling device through a body tube tree in the selecteddirection of travel until a stop instruction is received based onsensing a local parameter value with a parameter sensor. The motioncontrol instructions can cause the lumen traveling device to turn, tocontinue moving in the current direction, or reverse its direction. Inan embodiment, the motion control instructions can cause at least one ofthe steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to move in theselected direction of travel until a branch point is reached. Arrival ata branch point is detected using one or more arrival sensor as describedelsewhere herein.

FIG. 28E depicts further variants of selecting a direction of travelfrom the at least two directions of travel based at least in part on thedata representing at least one parameter value sensed from at least oneof the at least two possible directions of travel of the lumen travelingdevice through the body tube tree (2806). These include avoiding atleast one direction of travel if the data representing the at least oneparameter value sensed from the at least one direction of travelindicates that the at least one direction of travel is non-navigable bythe lumen traveling device (2850). Selecting the direction of travel caninclude selecting the direction of travel based on the value of afunction of the at least one parameter (2851), which can includeselecting the direction of travel having the lowest value of thefunction of the at least one parameter (2852), the highest value of thefunction of the at least one parameter (2853), or having a value of thefunction of the at least one parameter that falls within a specifiedrange of values (2854). The method can include selecting a direction oftravel from the at least two directions of travel based at least in parton the data representing parameter values sensed at two or more times bycomparing a rate of change of at least one parameter from the at leasttwo possible directions of travel and selecting the direction of travelhaving the lowest rate of change of the at least one parameter (2855).In an embodiment, the method can include selecting a direction of travelfrom the at least two directions of travel based at least in part on thedata representing parameter values sensed at two or more times bycomparing a rate of change of at least one parameter from the at leasttwo possible directions of travel and selecting the direction of travelhaving the highest rate of change of the at least one parameter (2856).

FIG. 28F depicts further additional steps (2810) which can be includedin method (2801). In an embodiment, additional step (2810) can includeidentifying a stop condition based at least in part on the datarepresenting at least one parameter value sensed from at least one ofthe at least two possible directions of travel of the lumen travelingdevice through the body tube tree; and directing at least one of thesteering mechanism and the propelling mechanism on the lumen travelingdevice to cause the lumen traveling device to stop moving through thebody tube tree (2860). In an embodiment, additional step (2810) caninclude storing the data representing at least one parameter valuesensed from at least one of the at least two possible directions oftravel of the lumen traveling device through the body tube tree in amemory location on the lumen traveling device (2861) storinginstructions related to directing at least one of the steering mechanismand the propelling mechanism on the lumen traveling device to causemovement of the lumen traveling device in a memory location on the lumentraveling device (2862) transmitting the data representing at least oneparameter value sensed from at least one of the at least two possibledirections of travel of the lumen traveling device through the body tubetree from the lumen traveling device to a remote device (2863)transmitting instructions related to directing at least one of thesteering mechanism and the propelling mechanism on the lumen travelingdevice to cause movement of the lumen traveling device from the lumentraveling device to a remote device (2864) receiving at least one ofinstructions or data from a remote device (2865). In another embodiment,method (2801) can include receiving information related to whether ornot at least one of at least two possible directions of travel of thelumen traveling device through the body tube tree has previously beentraveled by the lumen traveling device; and selecting the direction oftravel from the at least two possible directions of travel based atleast in part on the information related to whether or not at least oneof at least two possible directions of travel of the lumen travelingdevice through the body tube tree has previously been traveled by thelumen traveling device (2866).

FIG. 27 illustrates a block diagram of a system 2700 that includes a setof instructions 2704 for operating a lumen traveling device. Whilesystem 2700 is shown to include instructions for performing method 2800as described in connection with FIG. 28A, system 2700 can be modified toperform any method as depicted in FIGS. 28A-28F. An embodiment of system2700 is provided using non-transitory machine readable media 2702including a set of instructions 2704 including one or more instructionsthat cause the lumen traveling device control system to identify atleast two possible directions of travel of a lumen traveling devicethrough a body tube tree, the body tube tree including a plurality ofbranched, interconnected channels, and the at least two possibledirections of travel corresponding to at least two of the branched,interconnected channels; one or more instructions that cause the lumentraveling device control system to receive data representing at leastone parameter value sensed from at least one of the at least twopossible directions of travel of the lumen traveling device through thebody tube tree; one or more instructions that cause the lumen travelingdevice control system to select a direction of travel from the at leasttwo directions of travel based at least in part on the data; and one ormore instructions that cause the lumen traveling device control systemto direct at least one of the steering mechanism and the propellingmechanism on the lumen traveling device to cause the lumen travelingdevice to move through the body tube tree in the selected direction oftravel. The one or more instructions can be, for example, computerexecutable and/or logic implemented instructions. In an embodiment, thenon-transitory machine readable media 2702 may include computer readablemedia 2706. In an embodiment, the non-transitory machine readable media2702 can include recordable-type media 2708.

FIG. 30A illustrates a method 3000 of operating a lumen traveling devicein a lumen of a body tube tree including identifying at least twopossible directions of travel of a lumen traveling device through a bodytube tree, the body tube tree including a plurality of branched,interconnected channels, and the at least two possible directions oftravel corresponding to at least two of the branched, interconnectedchannels at 3002; receiving data representing a stored parameter valuerelating to a previous event at 3004; selecting a direction of travelfrom the at least two directions of travel based at least in part on thedata representing a stored parameter value relating to a previous eventat 3006; and directing at least one of a steering mechanism and apropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree in the selecteddirection of travel at 3008. This method can be performed, for example,with a device as depicted in and described in connection with FIGS. 1,2, 7 and 8.

FIG. 30B depicts method 3001, which is a variant of method 3000 depictedin FIG. 30A. In method 3001, step 3004 further can include receivingdata relating to a previous action performed by the lumen travelingdevice (3020). In some embodiments this can further include wherein theprevious action includes turning the lumen traveling device in a firstdirection, and wherein the data relating to the previous action includesdata representing the first direction (3021). Step 3004 can includereceiving data relating to a parameter value previously sensed by thelumen traveling device (3022). Method 3001 can also include anadditional step 3010, which in the example of FIG. 30B includesdetermining that at least one of the at least two directions of travelis non-navigable by the lumen traveling device; wherein the selecting adirection of travel from the at least two directions of travel based atleast in part on the data includes avoiding the at least one of the atleast two directions of travel if it is non-navigable by the lumentraveling device (3023).

As depicted in FIG. 30C, in further variants of the method 3001,additional step 3010 can include identifying a stop condition based atleast in part on the data; and directing at least one of the steeringmechanism and the propelling mechanism on the lumen traveling device tocause to cause the lumen traveling device to stop moving through thebody tube tree (3030). In an embodiment, additional step 3010 caninclude storing the data in a memory location on the lumen travelingdevice (3031), storing motion control instructions for directingoperation of at least one of the steering mechanism and the propellingmechanism in a memory location on the lumen traveling device (3032),transmitting the data from the lumen traveling device to a remote device(3033), transmitting motion control instructions for directing operationof at least one of the steering mechanism and the propelling mechanismfrom the lumen traveling device to a remote device (3034), and/orreceiving at least one of instructions or data from a remote device(3035). In another variant, additional step 3010 can include receivinginformation related to whether or not at least one of at least twopossible directions of travel of the lumen traveling device through thebody tube tree has previously been traveled by the lumen travelingdevice; and selecting the direction of travel from the at least twopossible directions of travel based at least in part on the informationrelated to whether or not at least one of at least two possibledirections of travel of the lumen traveling device through the body tubetree has previously been traveled by the lumen traveling device (3036).

As shown in FIG. 30D, directing at least one of the steering mechanismand the propelling mechanism on the lumen traveling device to cause thelumen traveling device to move through the body tube tree in theselected direction of travel for a pre-determined duration (3008) caninclude directing at least one of the steering mechanism and thepropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree in the selecteddirection of travel for a pre-determined distance (3040), directing atleast one of the steering mechanism and the propelling mechanism on thelumen traveling device to cause the lumen traveling device to movethrough the body tube tree in the selected direction of travel for apre-determined duration (3041), directing at least one of the steeringmechanism and the propelling mechanism on the lumen traveling device tocause the lumen traveling device to move through the body tube tree inthe selected direction of travel until an stop instruction is receivedfrom a remote device by the lumen traveling device (3042), directing atleast one of the steering mechanism and the propelling mechanism on thelumen traveling device to cause the lumen traveling device to turn(3043), directing at least one of the steering mechanism and thepropelling mechanism on the lumen traveling device to cause the lumentraveling device to continue moving in a current direction of travel(3044), and/or directing at least one of the steering mechanism and thepropelling mechanism on the lumen traveling device to cause to cause thelumen traveling device to reverse its direction of travel (3045).

In an embodiment, the lumen traveling device can be instructed to selecta direction of travel based on receiving data representing a storedparameter value relating to a previous event. The stored parameter valuerelating to a previous event can be a parameter value previously sensedby the lumen traveling device and can include values representative ofan anatomical feature of the lumen such as a branch point, a valve, apolyp, an aneurysm, growth, a tumor, obstruction; a man-made structuresuch as an implantable device of some sort, potentially includinganother lumen traveling device; or other parameters such as anelectrical field, magnetic field, temperature, flow condition, time,location, pressure, pH, presence or concentration of a chemical compoundor species. The stored parameter value can also include data regardingthe characterization of the branching elements of the body tube tree andposition indicator signals that have been used to inform development ofa map of at least a portion of the body tube tree. The stored parametervalue relating to a previous event can include data regarding previoustravel of the lumen traveling device along one or more portions of apre-existing and/or evolving map of a least a portion of the body tubetree.

In some embodiments, the previous event can be an action previouslyperformed by the lumen traveling device. Examples of performing anaction include but are not limited to releasing a material, releasing adevice or structure, releasing an energy, collecting a sample,collecting a device or structure, attaching a structure to a wall of thebody tube tree, delivering a material of structure to a receivingportion of a man-made device, receiving a material or structure from adelivery portion of a man-made device, receiving a signal from a remotesource, receiving power from a remote source, transmitting a signal to aremote location, performing a surgical step or procedure, removingtissue from at least a portion of the body tube tree, removing specificcomponents of at least a portion of a fluid from a body tube tree,exposing a catalyst, generating a localized electric field, generating alocalized magnetic field, producing heat, causing cooling, emittingelectromagnetic radiation, emitting acoustic energy, applying pressureto at least a portion of the body tube tree, modulating the flow of afluid through at least a portion of the body tube tree. An example of aprevious event can include placement of one or more chemical or physicalmarkers or labels which are now detectable by the lumen traveling deviceand are used to inform the selection of a direction of travel of thelumen traveling device.

The direction of travel of the lumen traveling device can be selectedbased on one or more stored parameter values. For example, the lumentraveling device may reach a branch point in the body tube tree andselect a direction of travel into the two or more branch channels basedon one or more stored parameter values indicating whether a particularchannel has been previously traveled. As another example, the lumentraveling device may reach a location in the lumen of the body tube treewhere one or more stored parameter values indicate that an action waspreviously performed, and may select a direction of travel based on thatinformation. Motion control instructions are generated to cause movementof the lumen traveling device in the selected direction of travel asdescribed herein.

FIG. 29 illustrates a block diagram of a system 2900 that includes a setof instructions 2904 for operating a lumen traveling device. Whilesystem 2900 is shown to include instructions for performing method 3000as described in connection with FIG. 30A, system 2900 can be modified toperform any method as depicted in FIGS. 30A-30D. An embodiment of thesystem 2900 is provided using non-transitory machine readable media 2902including a set of instructions 2904 including one or more instructionsthat cause the lumen traveling device control system to identify atleast two possible directions of travel of a lumen traveling devicethrough a body tube tree, the body tube tree including a plurality ofbranched, interconnected channels, and the at least two possibledirections of travel corresponding to at least two of the branched,interconnected channels; one or more instructions that cause the lumentraveling device control system to receive data representing a storedparameter value relating to a previous event associated with at leastone of the at least two possible directions of travel; one or moreinstructions that cause the lumen traveling device control system toselect a direction of travel from the at least two directions of travelbased at least in part on the data representing a stored parameter valuerelating to a previous event associated with at least one of the atleast two possible directions of travel; and one or more instructionsthat cause the lumen traveling device control system to direct at leastone of a steering mechanism and a propelling mechanism on the lumentraveling device to cause the lumen traveling device to move through thebody tube tree in the selected direction of travel. The one or moreinstructions may be, for example, computer executable and/or logicimplemented instructions. In an embodiment, the non-transitory machinereadable media 2902 can include computer readable media 2906. In anembodiment, the non-transitory machine readable media 2902 can includerecordable-type media 2908.

FIG. 32A illustrates a method 3200 of operating a lumen traveling devicein a lumen of a body tube tree including receiving data including atleast one target parameter value representing a target location towardwhich the lumen traveling device is to travel through a body tube treeincluding a plurality of branched, interconnected channels, the targetlocation being located within the body tube tree at 3202; sensing atleast one parameter value representative of a current location of thelumen traveling device at 3204; determining whether the current locationof the lumen traveling device is the target location at 3206; directingan active portion of the lumen traveling device to perform an action ifthe current location is the target location at 3208; or directing atleast one of a steering mechanism and a propelling mechanism on thelumen traveling device to cause the lumen traveling device to movethrough the body tube tree in a selected direction of travel if thecurrent location is not the target location at 3210.

FIG. 32B depicts method 3201, a variant of the method depicted in FIG.32A. As indicated generally at 3212, method 3201 can include one or moreadditional steps 3212.

In an embodiment, a lumen traveling device travels along a controlledpath that leads to a specific target location. The lumen travelingdevice receives information regarding a target parameter valuerepresenting a target location towards which the lumen traveling devicetravels through a body tube tree. The lumen traveling device furthersenses at least one parameter value representative of the currentlocation of the lumen traveling device. Sensors for sensing one or morelocal parameter values representative of a current location have beendescribed herein. One or more parameter values representative of thecurrent location are compared with the one or more target parametervalues representative of the target location to determine whether or notthe lumen traveling device has arrived at the target location. If thecurrent location is the target location, the lumen traveling device maybe instructed to perform an action. If the current location is not thetarget location, motion control instructions are generated to move thelumen traveling device in a selected direction of travel towards thetarget location. In a further embodiment, the steps of the method ofFIG. 32 comprise an iterative process in which parameter valuesrepresentative of a current location are measured and compared with thetarget parameter values representative of the target location, and thelumen traveling device is instructed to move to a new current locationwhereupon another set of parameter values representative of a currentlocation are measured and compared with the target parameter values.This iterative process may continue until the lumen traveling devicereaches the target location.

The lumen traveling device can receive data including at least onetarget parameter value representative of a target location. A targetlocation can be a final destination of the lumen traveling device, asindicated at 3214 in FIG. 32B. Alternatively, a target location can bean intermediate destination of the lumen traveling device, as indicatedat 3215 in FIG. 32B. The target location can include a location ofanatomical interest (e.g., a branching point, a valve), a location nearan organ, a tumor, an injury, etc., a diseased or damaged region (e.g. afistula or aneurysm), area of scar tissue, a polyp, a blockage orconstriction formed by a atherosclerotic plaque, blood clot, orvasospasm, for example. In an embodiment, the target location is aspecific location on a stored map of the body tube tree.

The target parameter representative of a target location can include,but is not limited to, a temperature, a pressure, a fluid flow, anoptical absorption, optical emission, fluorescence, or phosphorescence,an index of refraction, an electrical resistivity, a density or soundspeed, a pH, an osmolality, or a concentration, e.g., of an analyte. Theparameter can be representative of the presence or absence of anembolism, the presence or absence of an object (such as a blood clot, athrombus, an embolus, a plaque, a lipid, a kidney stone, a dustparticle, a pollen particle, a gas bubble, an aggregate, a cell, aspecific type of cell, a cellular component or fragment, a collection ofcells, a gamete, a pathogen, or a parasite), and/or the presence orabsence of a substance such as a biological marker, an antibody, anantigen, a peptide, a polypeptide, a protein, a complex, a nucleic acid,an oligonucleotide, a polynucleotide, a cell (and, in some cases, a cellof a particular type, e.g. by methods used in flow cytometry), acellular component, an organelle, a gamete, a pathogen, asignaling-material, a lipid, a lipoprotein, an alcohol, an acid, an ion,an immunomodulator, a sterol, a steroid, a carbohydrate, a sugar, apolysaccharide, a glycoprotein, a metal, an electrolyte, a metabolite,an organic compound, an organophosphate, a drug, a therapeutic, a gas, apollutant, a tag (e.g., chemical or physical marker or label), or acombination thereof.

The target location can be detected by sensing a target parameter valuerepresentative of the target location. The target parameter can includeone or more chemical markers or labels, chemical fingerprints, alteredmechanical, optical, thermal, electrical or acoustic properties, animage, and by other detectable parameter. In an embodiment, the targetparameter representative of a target location can be a change inautofluorescence or other optically detectable signal associated with acancer, an atherosclerotic plaque, other lesion or pathology. See, e.g.,Koenig et al., J. Fluoresc., 1994, 4:17-40; Chiyo et al., Lung Cancer2005, 48:307-313; and Weingandt et al., BJOG, 2002, 109:947-951, each ofwhich is incorporated herein by reference. In an embodiment, the targetparameter value representative of a target location may be an increaseand/or decrease in one or more chemical analytes associated with cancer,plaque, infection, or other lesion or pathology. As an example, thetarget parameter value may be an increase in magnetic properties of anatherosclerotic plaque relative to normal lumen wall due to increasedlevels of iron Fe(II) and Fe(III) cations associated with the plaque.See, e.g., Raman et al., JACC Cardiovasc., Imaging 2008, 1:49-57, whichis incorporated herein by reference. In an embodiment, the targetparameter can be a lesion along the lumen of the body tube tree visiblewith visible light imaging and an image capture device. In anembodiment, the target parameter can be a change in the diameter of thelumen of a body tube tree indicative of an occluding lesion such as, forexample, an atherosclerotic plaque, a polyp, or a cancerous lesion. In afurther embodiment, the target parameter can be a signal from a chemicalor physical marker or label previously placed at the target location. Asused herein, the term “lesion” refers not only to cancerous lesions, butto various other types of tissue damage or abnormality, e.g., scartissue, granuloma, infiltration, etc. A lesion may be caused by injuryor disease, for example. In some cases, a lesion may be bacterial orviral in origin.

As indicated at 3216 in FIG. 32B, in an embodiment, the method caninclude determining the current location of the lumen traveling devicefrom the at least one parameter value representative of a currentlocation of the lumen traveling device, wherein determining whether thecurrent location of the lumen traveling device is the target locationincludes comparing the current location of the lumen traveling devicewith the target location toward which the lumen traveling device is totravel.

The current location of the lumen traveling device can be determinedbased upon one or more sensed parameter values representative of thecurrent location. The parameter values representative of the currentlocation of the lumen traveling device can include chemical markers orlabels, chemical fingerprints, altered mechanical, optical, thermal,electrical or acoustic properties, an image, or other detectableparameters. Other parameters representative of a current location caninclude but are not limited to rate of fluid flow, direction of fluidflow, presence or concentration of a chemical or other analyte,concentration gradient, temperature, temperature gradient, luminaldimension, material in or on a lumen wall, lumen wall mechanicalproperty, a position indicator signal, an electromagnetic field,markers, or labels. As depicted in FIG. 32C, sensing at least oneparameter value representative of a current location of the lumentraveling device (3204) can include sensing at least one parameter valuerepresentative of an orientation of at least a portion of the body tubetree (3221), sensing at least one parameter value representative of anorientation of at least a portion of the body tube tree within aabsolute coordinate system (3222), sensing at least one parameter valuerepresentative of an orientation of at least a portion of the body tubetree within a relative coordinate system (3223), sensing at least oneparameter value representative of an orientation of at least a portionof the body tube tree relative to at least one other portion of the bodytube tree (3224), sensing at least one parameter value representative ofan orientation of at least a portion of the body tube tree relative toat least one other portion of the body tube tree (3225), sensing atleast one parameter value representative of a rate of fluid flow throughof at least a portion of the body tube tree (3226), sensing at least oneparameter value representative of a direction of fluid flow through ofat least a portion of the body tube tree (3227), sensing at least oneparameter value representative of a chemical (3228), sensing at leastone parameter value representative of at least one of a biologicalmarker, a biomaterial, a carbohydrate, a sugar, a cell, a cell fragment,a chemical, a chemokine, a hormone, a complex, a cytokine, a drug, agas, a lipid, a metabolite, a pathogen, a signaling-material, apolypeptide, a protein, a nucleic acid, an oligonucleotide, apolynucleotide, a sterol, a steroid, a therapeutic, an alcohol, anantibody, an electrolyte, an inflammatory molecule, or an ion (3229). Aparameter value representative of an analyte can be a parameter valuerepresentative of the presence or concentration of the analyte, forexample. In addition, as shown in FIG. 32D, sensing at least oneparameter value representative of a current location of the lumentraveling device (3204) can include sensing at least one parameter valuerepresentative of a concentration gradient of at least one of abiological marker, a biomaterial, a carbohydrate, a sugar, a cell, acell fragment, a chemical, a chemokine, a hormone, a complex, acytokine, a drug, a gas, a lipid, a metabolite, a pathogen, asignaling-material, a polypeptide, a protein, a nucleic acid, anoligonucleotide, a polynucleotide, a sterol, a steroid, a therapeutic,an alcohol, an antibody, an electrolyte, an inflammatory molecule, or anion (3230). Sensing at least one parameter value representative of acurrent location of the lumen traveling device (3204) can includesensing at least one parameter value representative of a temperature(3231) sensing at least one parameter value representative of atemperature gradient (3232), sensing at least one parameter valuerepresentative of a lumenal dimension (3233), sensing at least oneparameter value representative of a material in or on a lumen wall(3234), sensing at least one parameter value representative of a lumenwall mechanical property (3235), sensing at least one parameter valuerepresentative of a position signal (3236), sensing at least oneparameter value representative of an electromagnetic field (3237),and/or sensing at least one parameter value representative of a thepresence of a marker or label (3238).

Sensors for sensing one or more local parameter values representative ofa current location have been described herein. Sensing at least oneparameter value representative of a current location of the lumentraveling device can further include one or more instructions that causethe lumen traveling device control system to direct the sensing of atleast one parameter value representative of an orientation of at least aportion of the body tube tree within an absolute coordinate system, arelative coordinate system, and/or relative to at least one otherportion of the body tube tree.

In an embodiment, the method as depicted in FIG. 32A and variantsthereof can further include receiving data representing at least oneparameter value sensed from at least one of at least two possibledirections of travel of the lumen traveling device through the body tubetree; and selecting a direction of travel from the at least twodirections of travel based at least in part on the data representing atleast one parameter value sensed from at least one of the at least twopossible directions of travel of the lumen traveling device through thebody tube tree. The method can also include receiving informationindicating whether or not at least one of at least two possibledirections of travel of the lumen traveling device through the body tubetree has previously been traveled by the lumen traveling device andselecting a direction of travel from the at least two directions oftravel based at least in part on the information indicating whether ornot at least one of at least two possible directions of travel of thelumen traveling device through the body tube tree has previously beentraveled by the lumen traveling device.

As shown in FIG. 32E, determining whether the current location of thelumen traveling device is the target location (3206) can includecomparing the at least one parameter value representative of a currentlocation of the lumen traveling device with the at least one targetparameter value representing a target location toward which the lumentraveling device is to travel (3239). For example, the target parametervalue representing the target location can include a temperature (3240),a pressure (3241), a fluid flow (3242), an optical absorption (3243), anoptical emission (3244), a fluorescence (3245), a phosphorescence(3246), an index of refraction (3247), an electrical resistivity (3248),a density (3249), a sound speed (3250), a pH (3251), an osmolality orconcentration (3252). In an embodiment, the target parameter valuerepresenting the target location can include at least one oftemperature, pressure, fluid flow, optical absorption, optical emission,fluorescence, phosphorescence, index of refraction at least onewavelength, electrical resistivity, density, sound speed, pH,osmolality, or concentration (3253).

The value of one or more parameter values representative of the currentlocation can be compared with the value of one or more target parametervalues indicative of a target location to determine whether the currentlocation is the target location. The value of a parameter can includebut is not limited to a number, an image, a spectrum, a color, aprofile, a fingerprint, or a combination thereof. A mathematicalalgorithm, pattern recognition algorithm, pattern matching algorithm,microprocessor, software program, analog or digital comparator or logiccircuitry, and/or look-up table, for example, can be used to compareparameter values representative of a current location and parametervalues representative of a target location. Comparison of parametervalues representative of a current location and a target location can beperformed at least in part by the lumen traveling device. Alternatively,comparison of parameter values representative of a current location anda target location can be performed by a remote device and the results ofthe comparison transmitted back to the lumen traveling device.

If the current location is determined to be the target location,instructions can be sent to the active portion of the lumen travelingdevice to initiate performing an action. As shown in FIG. 32F, directingan active portion of the lumen traveling device to perform an action ifthe current location is the target location (3208) can include directingthe active portion of the lumen traveling device to perform variousdifferent actions. Actions to be performed at the target location caninclude but are not limited to releasing a material (3255), releasing adevice or structure (3257), releasing energy (3258), collecting a sample(3259) (which can include collecting at least one of a fluid sample or asample from a wall region of the body tube tree (3260)), collecting adevice or structure (3261), attaching a structure to a wall of the bodytube tree (3262), delivering a material or structure to a receivingportion of a man-made device (3263), receiving a material or structurefrom a delivery portion of a man-made device (3264), receiving a signalfrom a remote source (3265), which can be an encrypted signal, as shownat 1927 in FIG. 19, receiving power from a remote source (3266),transmitting a signal to a remote location (3267), which can be anencrypted signal, as shown at 1925 in FIG. 19, and performing a surgicalstep or procedure (3268). An action to be performed at a target locationcan include delivering a material to a wall region of the body tube tree(3298). As further shown in FIG. 32G, actions to be performed at thetarget location can include but are not limited to, removing tissue fromat least a portion of the body tube tree (3269), removing specificcomponents of at least a portion of a fluid from a body tube tree(3270), exposing a catalyst (3271), generating a localized electricfield (3272), generating a localized magnetic field (3273), producingheat (3274), causing cooling (3275), emitting electromagnetic radiation(3276), emitting acoustic energy (3277), applying pressure to at least aportion of the body tube tree (3278), modulating the flow of a fluidthrough at least a portion of the body tube tree (3279).

The method can further include sensing a second local parameter value,stopping performance of an action if the local parameter value is withina specified range, and initiating performance of an action if the localparameter value is within a specified range. For example, arrival of thelumen traveling device at a target location that is a cancerous lesionmay result in instructions being sent to an active portion of the lumentraveling device to perform an action that includes emitting an ablatingenergy or cutting and/or scraping to remove the cancerous lesion.

If the parameter value representative of the current location differsfrom the target parameter value representative of the target location,motion control instructions are generated to move the lumen travelingdevice in a selected direction of travel until the target location isreached. In an embodiment, the lumen traveling device randomly searchesfor the target location by comparing one or more parameter valuesrepresentative of the current location of the lumen traveling devicewith one or more parameter values representative of the target location.In this instance, the lumen traveling device moves through the body tubetree scanning the environment with one or more sensors and comparingparameter values representative of a current location with parametervalues representative of a target location until the target location isfound. Upon arriving at the target location, the lumen traveling devicemay be instructed to perform one or more actions, examples of which havebeen described herein.

As shown in FIG. 32H, directing at least one of a steering mechanism anda propelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree in a selecteddirection of travel if the current location is not the target location(3210) can include directing at least one of the steering mechanism andthe propelling mechanism on the lumen traveling device to cause thelumen traveling device to stop (3280), directing at least one of thesteering mechanism and the propelling mechanism on the lumen travelingdevice to cause the lumen traveling device to advance (3281), directingat least one of the steering mechanism and the propelling mechanism onthe lumen traveling device to cause the lumen traveling device toreverse direction (3282), or directing at least one of the steeringmechanism and the propelling mechanism on the lumen traveling device tocause the lumen traveling device to turn (3283).

As shown in FIG. 32I, addition step 3212 can include receiving map datarepresenting a map of at least a portion of the body tube tree (3284),which can include receiving map data from a data storage location on thelumen traveling device (3285) or receiving map data from a remote source(3286). Map data from a remote source can be encrypted, as indicated at3297. In an embodiment, additional step (3212) can include receivingdata representing at least one parameter value sensed from at least oneof at least two possible directions of travel of the lumen travelingdevice through the body tube tree and selecting a direction of travelfrom the at least two directions of travel based at least in part on thedata (3287). In this embodiment, selecting the direction of travel fromthe at least two directions of travel based at least in part on the datacan include avoiding at least one of the at least two directions oftravel if at least one of the at least two directions of travel isnon-navigable by the lumen traveling device (3288). In an embodiment,additional step (3212) can include receiving information indicatingwhether or not at least one of at least two possible directions oftravel of the lumen traveling device through the body tube tree haspreviously been traveled by the lumen traveling device; and selecting adirection of travel from the at least two directions of travel based atleast in part on the information indicating whether or not at least oneof at least two possible directions of travel of the lumen travelingdevice through the body tube tree has previously been traveled by thelumen traveling device (3289). FIG. 32J includes still furtheradditional steps that may be included in methods 3200 or 3201. Furtheradditional steps 3212 include storing the data in a memory location onthe lumen traveling device (3289), storing motion control instructionsfor directing operation of at least one of the steering mechanism andthe propelling mechanism in a memory location on the lumen travelingdevice (3290), transmitting the data from the lumen traveling device toa remote device (3291), transmitting motion control instructions fordirecting operation of at least one of the steering mechanism and thepropelling mechanism from the lumen traveling device to a remote device(3292), receiving at least one of instructions or data from a remotedevice (3293), determining the current location of the lumen travelingdevice on a map of at least a portion of a body tube tree, the lumentraveling device located within the body tube tree represented by themap; and planning a path of travel for the lumen traveling device, thepath of travel leading at least a portion of the way between the currentlocation and the target location, wherein directing at least one of asteering mechanism and a propelling mechanism on the lumen travelingdevice to cause the lumen traveling device to move through the body tubetree in a selected direction of travel if the current location is notthe target location along the planned path of travel (3294).Instructions or data received from a remote device can be encrypted, asindicated at 3299.

FIG. 31 illustrates a block diagram of a system 3100 that includes a setof instructions 3104 for operating a lumen traveling device such as thatdepicted in and described in connection with FIGS. 1, 2, 7 and 8. Whilesystem 3100 is shown to include instructions for performing method 3200as described in connection with FIG. 32A, system 3100 can be modified toperform any method as depicted in FIGS. 32A-32J. An embodiment of system3100 is provided using non-transitory machine readable media 3102including a set of instructions 3104 including one or more instructionsthat cause the lumen traveling device control system to receive dataincluding at least one target parameter value representing a targetlocation in a body tube tree, the body tube tree including a pluralityof branched, interconnected channels, the target location being locatedwithin the body tube tree; one or more instructions that cause the lumentraveling device control system to direct the sensing of at least oneparameter value representative of a current location of the lumentraveling device within the body tube tree; one or more instructionsthat cause the lumen traveling device control system to determinewhether the current location of the lumen traveling device is the targetlocation; one or more instructions that cause the lumen traveling devicecontrol system to direct an active portion of the lumen traveling deviceto perform an action if the current location is the target location; andone or more instructions that cause the lumen traveling device controlsystem to direct at least one of a steering mechanism and a propellingmechanism on the lumen traveling device to cause the lumen travelingdevice to move through the body tube tree in a selected direction oftravel if the current location is not the target location. The one ormore instructions may be, for example, computer executable and/or logicimplemented instructions. In an embodiment, the non-transitory machinereadable media 3102 can include computer readable media 3106. In anembodiment, the non-transitory machine readable media 3102 can includerecordable-type media 3108.

FIG. 34A illustrates a method 3400 of operating a lumen traveling devicein the lumen of a body tube tree including obtaining a map of at least aportion of a body tube tree including a plurality of branched,interconnected channels at 3402; determining a current location of alumen traveling device on the map with an operation performed on-boardthe lumen traveling device, the lumen traveling device located withinthe body tube tree represented by the map at 3404; determining a targetlocation for the lumen traveling device within the body tube tree at3406; planning a path of travel for the lumen traveling device, theplanned path of travel leading at least a portion of the way between thecurrent location and the target location at 3408; and causing movementof the lumen traveling device through the body tube tree along the pathof travel at 3410. This method can be performed, for example, with adevice as depicted in and described in connection with FIGS. 1, 2, 7 and8.

A variant of this method is shown in FIG. 34B. FIG. 34B illustratesmethod 3401 of operating a lumen traveling device in the lumen of a bodytube tree including obtaining a map of at least a portion of a body tubetree including a plurality of branched, interconnected channels at 3402;determining a current location of a lumen traveling device on the mapwith an operation performed on-board the lumen traveling device, thelumen traveling device located within the body tube tree represented bythe map at 3404; determining a target location for the lumen travelingdevice within the body tube tree at 3406; planning a path of travel forthe lumen traveling device, the planned path of travel leading at leasta portion of the way between the current location and the targetlocation at 3408; and causing movement of the lumen traveling devicethrough the body tube tree along the path of travel at 3410, asdescribed in connection with FIG. 34A. Method 3401 further includessensing at least one parameter value with at least one sensor on thelumen traveling device at 3412; and performing a further operation withthe lumen traveling device based upon the at least one sensed parametervalue at 3414.

A further variant of this method is shown in FIG. 34C. FIG. 34Cillustrates method 3403 of operating a lumen traveling device in thelumen of a body tube tree including obtaining a map of at least aportion of a body tube tree including a plurality of branched,interconnected channels at 3402; determining a current location of alumen traveling device on the map with an operation performed on-boardthe lumen traveling device, the lumen traveling device located withinthe body tube tree represented by the map at 3404; determining a targetlocation for the lumen traveling device within the body tube tree at3406; planning a path of travel for the lumen traveling device, theplanned path of travel leading at least a portion of the way between thecurrent location and the target location at 3408; and causing movementof the lumen traveling device through the body tube tree along the pathof travel at 3410, as described in connection with FIG. 34A. Method 3403further includes sensing at least one parameter value with at least onesensor on the lumen traveling device at 3416; determining that at leasta portion of the planned path of travel is non-navigable by the lumentraveling device based on the at least one sensed parameter value at3418; and revising the planned path of travel to avoid the non-navigableportion of the planned path of travel at 3420.

In some aspects the lumen traveling device navigates through the bodytube tree of a subject based on the current location of the lumentraveling device relative to a map of the body tube tree. The locationof the lumen traveling device can be correlated with a pre-existing mapof the body tube tree of the subject, or used to construct a map of thebody tube tree of the subject. In an embodiment, a pre-existing map ofthe body tube tree of a subject is stored within a data storage locationof the lumen traveling device. The pre-existing map can be loaded intothe data storage location of the lumen traveling device prior tointroducing the lumen traveling device into a body tube tree of asubject, or it can be transmitted from a data storage location of aremote device through a wireless communication link to the data storagelocation of the lumen traveling device already residing in the lumen ofa body tube tree of a subject. In an embodiment, the pre-existing map ofthe body tube tree can reside entirely in the data storage location of aremote device.

As shown in FIG. 34D, with regard to obtaining a map of at least aportion of a body tube tree including a plurality of branched,interconnected channels at 3402, the map can include a topological map(3421), a metric map (3422), or a conformal map (3440), for example.Obtaining a map can include generating a map of at least a portion ofthe body tube tree through exploration of the body tube tree with thelumen traveling device 3423, receiving a map of at least a portion ofthe body tube tree from a remote source 3424, or receiving a map of atleast a portion of the body tube tree from another lumen travelingdevice 3425. As also shown in FIG. 34D, methods 3400, 3401, and 3403 asshown in FIGS. 34A, 34B, and 34C, respectively, can include determininga target location for the lumen traveling device within the body tubetree (3406), wherein determining a target location for the lumentraveling device within the body tube tree includes receiving at leastone instruction regarding a target location from a remote device (3426).

In an embodiment, a map of the body tube tree can be generated on thebasis of information gathered as the lumen traveling device travelsthrough the body tube tree of the subject. The map can be generatedeither with the use of logic on the lumen traveling device, logic in aremote device, or a combination thereof. The map thus generated can bestored in a memory location on the lumen traveling device or elsewhere.

FIG. 34E illustrates various aspects of, planning a path of travel forthe lumen traveling device, the planned path of travel leading at leasta portion of the way between the current location and the targetlocation (at 3408). In an embodiment, planning a path of travel for thelumen traveling device can include planning a path between the currentlocation and the target location (3427), where, for example, the targetlocation is a selected anatomical location (3428). In an embodiment,planning a path of travel for the lumen traveling device can includeplanning a path between the current location and a second location inthe body tube tree, the second location intermediate between the currentlocation and the target location on a map of the body tube tree (3429),e.g., planning a path between a first branch point at the currentlocation and a second branch point at the second location (3430).

In an embodiment, planning a path of travel can include planning a firstpath of travel leading between the current location and an intermediatelocation and a planning a second path of travel leading between theintermediate location and the target location and wherein causingmovement of the lumen traveling device through the body tube tree alongthe path of travel includes causing the lumen traveling device to movealong the first path of travel leading between the current location andan intermediate location and causing the lumen traveling device to movealong the second path of travel leading between the intermediatelocation and the target location (3431). In an embodiment, causing thelumen traveling device to move along the first path of travel caninclude controlling the movement of the lumen traveling device accordingto a first algorithm and causing the lumen traveling device to movealong the second path of travel includes controlling the movement of thelumen traveling device according to a second algorithm, wherein thefirst algorithm is different than the second algorithm (3432); forexample, the first algorithm can be a Markov localization algorithm andthe second algorithm can be a Kalman filtering algorithm (3433). In amethod including step 3431, obtaining a map of at least a portion of abody tube tree can include receiving the map of at least a portion of abody tube tree from a remote device (3434), receiving the map of atleast a portion of a body tube tree from a data storage location on thelumen traveling device (3435), or wherein obtaining a map of at least aportion of a body tube tree includes generating a map of at least aportion of the body tube tree through exploration of the body tube treewith the lumen traveling device (3436).

FIG. 33 illustrates a block diagram of a system 3300 that includes a setof instructions 3304 for operating a lumen traveling device, such as adevice as depicted in and described in connection with FIGS. 1, 2, 7 and8. While system 3300 is shown to include instructions for performingmethod 3400 as described in connection with FIG. 34A, system 3400 can bemodified to perform any method as depicted in FIGS. 34A-34E. Anembodiment of system 3300 is provided using non-transitory machinereadable media 3302 including a set of instructions 3304 including oneor more instructions that cause the lumen traveling device controlsystem to obtain a map of at least a portion of a body tube treeincluding a plurality of branched, interconnected channels; one or moreinstructions that cause the lumen traveling device control system todetermine a current location of a lumen traveling device on the map withan operation performed on-board the lumen traveling device, the lumentraveling device located within the body tube tree represented by themap; one or more instructions that cause the lumen traveling devicecontrol system to determine a target location for the lumen travelingdevice within the body tube tree; one or more instructions that causethe lumen traveling device control system to determine a path of travelfor the lumen traveling device, the path of travel leading at least aportion of the way between the current location and the target location;and one or more instructions that cause the lumen traveling devicecontrol system to direct at least one of a steering mechanism and apropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree along the path oftravel. The one or more instructions may be, for example, computerexecutable and/or logic implemented instructions. In an embodiment, thenon-transitory machine readable media 3302 can include computer readablemedia 3306. In an embodiment, the non-transitory machine readable media3302 can include recordable-type media 3308. The non-transitory machinereadable media 3302 can further include instructions that cause thelumen traveling device control system to read map data from a datastorage location on the lumen traveling device.

A map of at least a portion of the body tube tree can be obtained by thelumen traveling device itself using a combination of exploration,localization and mapping as outlined in FIG. 14. Alternatively, a map ofat least a portion of the body tube tree can be obtained through acombination of external imaging of the body tube tree and computationalanalysis to develop a three-dimensional structure and map of the bodytube tree. FIG. 35 outlines the steps for generating a map of a bodytube tree with external medical imaging 3500 including performing a scan(e.g., magnetic resonance imaging, computed tomography) at step 3502;generating a computer model of the three-dimensional structure of thebody tube tree at step 3504; generating a topological map (e.g.,branched node tree), including data on distance between nodes, usingcomputational modeling at step 3506; loading the map data into the lumentraveling device navigation system (either on-board or in remote device)at step 3508, inserting the lumen traveling device into the body tubetree at step 3510; and controlling navigation of the lumen travelingdevice from node to node at step 3512. Controlling navigation of thelumen traveling device from node to node at step 3512 can furtherinclude using a measurement device (e.g., ultrasound, arrival sensor) tosense and measure branches at junctions at step 3514; measuring distancetraveled from one node to the next while traveling through the body tubetree at step 3516; combining data from map, idiothetic sensing (e.g.,distance traveled, inertial measurements, lumen diameter), localparameter sensing and position indicator signals to localize lumentraveling device in the lumen node tree (e.g., confirm location) at step3518; and updating and correcting the map as needed at step 3520.

A map of a body tube tree can be based on two-dimensional and/orthree-dimensional renderings of images of a body tube tree generated byexternal medical imaging. Examples of medical imaging for use ingenerating two-dimensional and three-dimensional images of a body tubetree include but are not limited to X-ray, gamma camera, computedtomography (CT), magnetic resonance imaging (MRI), and ultrasound.Additional imaging methods include diffuse optical tomography,elastography, electrical impedance tomography, optoacoustic imaging,optical coherence tomography and scanning laser ophthalmoscopy.

A three-dimensional rendering of the vasculature, for example, can begenerated using magnetic resonance imaging. A variety of magneticresonance angiography imaging techniques can be used to generate imagesof the vasculature, based on flow effects or on inherent orpharmaceutically induced contrast. Examples of magnetic resonanceangiography (MRA) techniques include but are not limited to contrastenhanced MRA, time-of-flight (TOF) or inflow angiography, phase-contrastMRA, and fresh blood imaging. For contrast enhanced MRA, a contrastagent is injected into a vein and images are acquired during the firstpass of the agent through the arteries. Alternatively, the contrastagent can be a compound that resides for some time in the blood allowingfor imaging of both arteries and veins. Examples of contrast agents usedfor this purpose include but are not limited to gadolinium chelates,iron oxide (e.g., superparamagnetic and ultra-small superparamagneticiron oxide), and manganese chelates. As an example, Nowinski et al.,describe using magnetic resonance angiographic data to create a threedimensional atlas of the cerebral vasculature (Nowinski et al.,RadioGraphics, 2005, 25:263-271, which is incorporated herein byreference).

The scanned images of a body tube tree (e.g., vasculature) derived frommedical imaging can be compiled to generate a three-dimensional map ofthe body tube tree. The three-dimensional rendering can be transformedinto a nodal map system. For example, Tang & Chung describe using acenterline extraction technique to generate a branch map of thevasculature from a pre-segmented, three-dimensional rotationalangiography dataset (Tang & Chung, “Cerebral vascular tree matching of3D-RA data based on tree edit distance,” In, Medical Imaging andAugmented Reality, G. Z. Yang et al. (Eds): MIAR 2006, LNCS 4091, pp.116-123, Springer-Verlag Berlin Heidelberg, 2006, which is incorporatedherein by reference). Methods have also been described for definingvessel “trees” from three-dimensional image data captured by computedtomography, three-dimensional digital subtraction angiography,ultrasound, and confocal microscopy (see, e.g., Bullitt & Aylward,“Anaylsis of time-varying images using 3D vascular models,” Proceedings30th Applied Imagery Pattern Recognition Workshop (AIPR 2001), Bilof, R.and Palagi, L. (eds), IEEE Computer Society, Piscataway N.J., pp. 9-14,which is incorporated herein by reference).

FIG. 36 illustrates an example of a closed loop nodal map system 3600representative of the vasculature system in which a continuous path oftravel eventually leads back to node 1 at the “root” of the tree 3602.In this example, the “root” of the tree 3602 is the heart. Nodal mapsystem 3600 begins at the “root” of the tree 3602 and goes throughprogressive branches (e.g., nodes 3604) eventually reaching the nodes3604 representative of a capillary bed 3606 at which point the branchesbegin to converge and lead back to the “root” of the tree 3602. In thisexample, solid arrows 3608 represent flow away from the “root” of thetree 3602 (e.g., arterial blood flow) and dashed arrows 3610 representflow towards the “root” of the tree 3602 (e.g., venous blood flow). Fora lumen traveling device configured to fit into the capillary bed 3606,the “end” nodes for the out-bound (e.g., arterial) flow can be connectedto nodes of the in-bound (e.g., venous) flow. As an example, planning apath using the nodal map system 3600 from the “root” of the tree 3602 totarget location 3612 would involve following a path from node 1, to node2, to node 3, to node 7 to node 33, to node 38 at target location 3612.

Similarly, a three-dimensional volume rendering of the bronchial treecan be generated by using three-dimensional reconstruction software tostack multiple scanned images (e.g., slices) of the lung. For example,Yu et al. describe a system for complete definition and quantitativeanalysis of anatomical trees contained in high-resolutionthree-dimensional digital images (Yu et al., Comput. Biol. Med., 2007,37:1802-1820, which is incorporated herein by reference). Softwarepackages for 3D reconstruction of medical images are available fromcommercial sources (e.g., Amira® 5, Visage Imaging™ La Jolla, Calif.;Voxar 3D, Toshiba Medical Visualization Systems Europe, Ltd., Edinburgh,UK). Skeletonizing or thinning algorithms can be used to generate askeleton or straight line central axis tree from the three-dimensionalvolume rendering of the bronchial tree. This in turn can be used togenerate a branched nodal map. As an example, Pisupati et al. describeusing a two pass algorithm to compute the central axis tree and toobtain accurate centroid points that lie along the axes of the branches(Pisupati et al., “A central axis algorithm for 3D bronchial treestructures,” ISCV, pp. 259-264, Proceedings of the InternationalSymposium on Computer Vision, 1995, which is incorporated herein byreference). The centroid points at each bifurcation are used to computethe branch points and three direction vectors along the branches. Thecentral axis tree is formed by connecting the computed branch points ateach bifurcation with straight lines. Also see, e.g., Kitaoka et al., J.Appl. Physiol., 1999, 87:2207-2217; Schertler et al., AJR 2004,183:83-89; and Zrimec & Busayarat, “3D Modeling and Visualization of theHuman Lung” 3dpvt, pp. 110-115, Second International Symposium on 3DData Processing, Visualization and Transmission (3DPVT'04), 2004, eachof which is incorporated herein by reference.

FIG. 37 illustrates an example of an open nodal map system 3700representative of the bronchial system in which a path of travel beginsat the “root” of the tree 3702 and goes through progressive branches(e.g., nodes 3704) eventually reaching “end nodes” 3706 at which pointtravel must continue in the reverse direction. In this example, the“root” of the tree 3702 can be the trachea, mouth or other entry wayinto the bronchial airways while the “end nodes” 3706 can be theterminal portion of the alveoli. Solid arrows 3708 indicate direction offlow from the “root” of the tree 3702 to the “end nodes” 3706. As anexample, planning a path using the nodal map system 3700 from the “root”of the tree 3702 to target location 3710 would involve following a pathfrom node 1, to node 2, to node 3, to node 6 to node 21, to node 27 attarget location 3710. The open nodal map system 3700 can also berepresentative of other maps of body tube trees in which the branchingpattern eventually reaches a dead-end, such as the case in which thelumen traveling device is not configured to travel into the capillariesof the vasculature and must reverse direction to continue moving.

A map generated using medical imaging can be stored on the lumentraveling device in a data storage location. Alternatively, the map canbe stored in a remote device, which is in communication with the lumentraveling device through a wireless transmitter/receiver system. As thelumen traveling device moves through the lumen of the body tube tree,one or more position indicator signals can be used to locate the lumentraveling device on the map. In addition, as the lumen traveling deviceexplores and senses the local environment, information regardingspecific characteristics of the branch channels as well as sensed localparameter values can be added to the map.

Information regarding the current location of the lumen traveling devicewithin the body tube tree can be determined using an operation performedon-board the lumen traveling device. For example, the lumen travelingdevice can receive one or more position indicator signals that indicatewhere the current location of the lumen traveling device is on thestored map. Similarly, the lumen traveling device can receiveinformation from one or more sensors regarding local parameter valuesthat are correlated with specific locations on the stored map.

The lumen traveling device can be instructed to navigate from a currentlocation to a target location within the body tube tree of a subject,whereupon the lumen traveling device performs one or more actions. Atarget location can be the final destination of the lumen travelingdevice. Alternatively, a target location can be an intermediatedestination of the lumen traveling device. A target location can includea location of anatomical interest (e.g., a branching point, a valve), alocation near an organ, a tumor, an injury, etc., a diseased or damagedregion (e.g. a fistula or aneurysm), an area of scar tissue, a polyp, ora blockage or constriction formed by a atherosclerotic plaque, bloodclot, or vasospasm, for example. In an embodiment, the target locationis a specific location on a stored map of the body tube tree which canbe identified by the lumen traveling device or by using an externalimaging technique. For example, the target location may be a suspiciouslesion in the bronchial body tube tree detected using chest radiography,computed tomography, magnetic resonance imaging, positron emissiontomography, or combinations thereof (see, e.g., Hollings & Shaw, Eur.Respir. J., 2002, 19:772-742, which is incorporated herein byreference). The target location, as identified by an external imagingtechnique, can be located on the stored map.

The map of the body tube tree obtained by exploration of the lumentraveling device and or by external medical imaging can be used to plana path of travel between a current location of the lumen travelingdevice and a target location. The lumen traveling device can beconfigured to receive instructions regarding the planned path of travelfrom on-board control circuitry or from a remote device. The lumentraveling device is instructed to move through the body tube tree alongthe planned path of travel. The current location of the lumen travelingdevice is determined at intervals and compared with the map of the bodytube tree, the planned path of travel and the target location.Corrections can be made in the planned path of travel and/or in themovements of the lumen traveling device to keep the lumen travelingdevice moving on course towards the target location. When the currentlocation of the lumen traveling device on the map is the targetlocation, the lumen traveling device may be instructed to stop andperform an action.

FIG. 38 shows various strategies for planning a path of travel 3800 of alumen traveling device through a body tube tree including planning apath to a specific location 3802 by planning an optimal path to a targetlocation based on known graph-search-based planning techniques (i.e., amap) 3804; planning a path along a gradient of a specific parameter 3806by choosing a local branch and or a direction that leads in the desireddirection along a gradient of specific parameter 3808; planning a pathbased on previous event 3810 by planning a path based on whether thedirection has been previously traveled 3812 and/or by planning a pathbased on previous action, movement, and or previously sensed parameter3814; and in some instances, planning a ‘random’ walk 3816 by choosingbranch and or direction of travel substantially at random 3818.

In an embodiment, rather than generating and/or storing a map, the lumentraveling device and/or remote device thereof can be configured to storeother positional or locational information that can be used to controlthe route taken by the lumen traveling device through the body tubetree. In an embodiment, the lumen traveling device can be configured tocover some statistical distribution of lumen sizes or locations duringits travels, but not necessarily travel a specific route through thebody. The size and location information for already-visited sites can bestored and used in selection of the route to be taken by the lumentraveling device.

FIG. 39 illustrates a block diagram of a system 3900 that is a variantof the system shown in FIG. 33, and that includes a set of instructions3904 for operating a lumen traveling device. An embodiment of system3900 is provided using non-transitory machine readable media 3902including a set of instructions 3304 as in FIG. 33, including one ormore instructions that cause the lumen traveling device control systemto obtain a map of at least a portion of a body tube tree including aplurality of branched, interconnected channels; one or more instructionsthat cause the lumen traveling device control system to determine acurrent location of a lumen traveling device on the map with anoperation performed on-board the lumen traveling device, the lumentraveling device located within the body tube tree represented by themap; one or more instructions that cause the lumen traveling devicecontrol system to determine a target location for the lumen travelingdevice within the body tube tree; one or more instructions that causethe lumen traveling device control system to plan a path of travel forthe lumen traveling device, the path of travel leading at least aportion of the way between the current location and the target location;and one or more instructions that cause the lumen traveling devicecontrol system to direct at least one of a steering mechanism and apropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree along the path oftravel. As shown in FIG. 39, the non-transitory machine readable mediafurther includes instructions 3904 specifying wherein the one or moreinstructions that cause the lumen traveling device control system toplan a path of travel for the lumen traveling device include one or moreinstructions that cause the lumen traveling device control system todetermine a first path of travel leading between the current locationand an intermediate location; and one or more instructions that causethe lumen traveling device control system to determine a second path oftravel leading between the intermediate location and the targetlocation. The one or more instructions may be, for example, computerexecutable and/or logic implemented instructions. In an embodiment, thenon-transitory machine readable media 3902 can include computer readablemedia 3906. In an embodiment, the non-transitory machine readable media3902 can include recordable-type media 3908.

FIG. 40 illustrates a method 4000 including obtaining a map of at leasta portion of a body tube tree including a plurality of branched,interconnected channels at 3402; determining a current location of alumen traveling device on the map with an operation performed on-boardthe lumen traveling device, the lumen traveling device located withinthe body tube tree represented by the map at 3404; determining a targetlocation for the lumen traveling device within the body tube tree at3406; planning a path of travel for the lumen traveling device, theplanned path of travel leading at least a portion of the way between thecurrent location and the target location at 3408; and causing movementof the lumen traveling device through the body tube tree along the pathof travel at 3410, where it is further specified at 4008 whereinplanning the path of travel for the lumen traveling device includesplanning a first path of travel leading between the current location andan intermediate location and a planning a second path of travel leadingbetween the intermediate location and the target location and whereincausing movement of the lumen traveling device through the body tubetree along the path of travel includes causing the lumen travelingdevice to move along the first path of travel leading between thecurrent location and an intermediate location and causing the lumentraveling device to move along the second path of travel leading betweenthe intermediate location and the target location.

Controlling the movement of the lumen traveling device along a firstpath between the current location and an intermediate location caninclude controlling the movement of the lumen traveling device accordingto a first algorithm. Controlling the movement of the lumen travelingdevice along a second path between the intermediate location and atarget location can include controlling the movement of the lumentraveling device according to a second algorithm. In an embodiment, thefirst algorithm and the second algorithm for controlling movement of thelumen traveling device along a first and a second path are the same. Inan embodiment, the first algorithm and the second algorithm forcontrolling movement of the lumen traveling device along a first and asecond path differ. For example, the first algorithm can be a Markovlocalization algorithm and the second algorithm can be a Kalmanfiltering algorithm.

The first and second algorithms for controlling movement of a lumentraveling device based on a map of a body tube tree can includeprobabilistic frameworks, Bayesian frameworks, artificial neuralnetworks, Cartesian symbolic-oriented approaches, Markov localization,simultaneous localization and mapping (SLAM), concurrent mapping andlocalization (CML), and expectation maximization. See, e.g., Thrun,“Robotic Mapping: A Survey,” In Exploring Artificial Intelligence in theNew Millenium, eds. Lakemeyer, G & Nebel, B, published by MorganKaufmann, 2002; Thrun, AI Magazine, 2000, 21:93-109; Pfister et al.,“Weighted line fitting algorithms for mobile robot map building andefficient data representation,” Proceedings of the 2003 IEEEInternational Conference on Robotics and Automation, Taipei, Taiwan,Sep. 14-19, 2003; Thrun et al., “A real-time algorithm for mobile robotmapping with applications to multi-robot and 3D mapping,” Proceedings ofthe 2000 IEEE International Conference on Robotics and Automation, SanFrancisco, Calif., April 2000, each of which is incorporated herein byreference.

PROPHETIC EXAMPLES Prophetic Example 1 Detecting and TreatingAtherosclerotic Plaques in the Vasculature with a Lumen Traveling Device

A method for detecting and treating atherosclerotic plaques in thevasculature of a mammalian subject may be performed with a systemincluding at least one lumen traveling device configured to travelthrough the vasculature, sense an atherosclerotic plaque, andcontrollably perform an action to treat the atherosclerotic plaque.Atherosclerotic plaques constitute focal accumulation of lipid, smoothmuscle cells, foamy macrophages, other inflammatory cells, andcholesterol crystals. Atherosclerotic plaque formation occurspredominantly in arteries and disproportionately in large arteries atpoints in the lumen where blood flow slows or is more turbulent such as,for example, at branch points or curved portions of the vasculature. Asthe plaque grows, the lumen of the arterial vessel is graduallyoccluded, restricting the flow of blood through the vessel. In someinstances, the plaque may rupture, inducing the formation of a thrombusat the site of the rupture that further occludes the vessel.Alternatively, debris associated with the ruptured plaque can traveldownstream and form an embolus that blocks an artery, e.g., a coronaryartery, leading to myocardial infarction and other acute coronarysyndromes. The ability to detect and treat vulnerable atheroscleroticplaques prior to rupture is of benefit to the subject.

The method of detecting and treating an atherosclerotic plaque includesintroducing one or more lumen traveling devices into one or more bloodvessels of a subject. In this example, a lumen traveling device isinitially placed into a large artery, e.g., the femoral artery, coronaryartery, or carotid artery, by directly injecting the lumen travelingdevice into the artery with a syringe fitted with a needle. The gauge ofneedle used for injection should be sufficient to allow passage of thelumen traveling device. Needles commonly used in medical practice rangein size from 10 gauge (nominal inner diameter of 2.69 millimeters) to 33gauge (nominal inner diameter of 0.11 millimeters). For example, thestandard nominal inner diameter of a 14 gauge needle is 1.6 millimeters.

FIG. 41A provides an illustrative example of a lumen traveling devicemoving through the vasculature body tube tree sensing the presence ofatherosclerotic plaques. FIG. 41B further provides an illustrativeexample of a lumen traveling device performing an action to eliminate anatherosclerotic plaque. In this example, lumen traveling device 4100moving through a body lumen 4102 can have a capsule-like body structure4103 and include a propelling mechanism 4105. Lumen traveling device4100 can include a sensor 4106, response control circuitry 4110, andreservoir 4112, the active portion of the lumen traveling device whichreleases a therapeutic agent for treatment of an atherosclerotic plaque.Lumen traveling device 4100 can also include motion control circuitry4114 to control movement of the lumen traveling device through thevasculature body tube tree. The sensor 4106 of the lumen travelingdevice can include a light emitting diode, which serves as anelectromagnetic radiation source that emits a first wavelength(s) ofelectromagnetic radiation 4116 to induce autofluorescence of a plaque4108 associated with the lumen wall 4104. The autofluorescence emittedby the plaque 4108 can be detected by an image capturing portion ofsensor 4106. Upon detection of the plaque 4108, reservoir 4112 can beactivated as shown in FIG. 41B. In this example, reservoir 4112 releasesa plaque stabilizing agent 4118, e.g., everolimus, which serves atherapeutic agent for treatment of an atherosclerotic plaque, in thiscase, by stabilizing the plaque 4108.

The lumen traveling device travels to a target location within thevasculature guided by a map. A map of the arterial vasculature can begenerated using external imaging as exemplified by magnetic resonanceangiography (MRA). In preparation for magnetic resonance angiography,the subject can be injected intravenously with a gadolinium-basedcontrast agent, e.g., gadodiamide (Omniscan™; dosed at 0.05 to 0.2mmol/kg). Magnetic resonance imaging can be performed using standardmethodologies. A stack of image slices can be generated representing aunique 3D volume of the subject's body. Computational analysis can beused to generate a topological map of the vasculature. At least aportion of the map is incorporated into the data storage location withinthe lumen traveling device with the remainder of the map incorporatedinto a remote device in wireless communication with the lumen travelingdevice.

The location of the lumen traveling device within the vascular body tubetree of a subject can be determined relative to the map of the vascularbody tube tree. In this example, a position indicator signal is producedby a radiofrequency identification (RFID) tag associated with the lumentraveling device. The RFID tag produces (reflects or transmits) a signalthat is detected by an external receiver in response to an interrogationsignal generated by the remote device.

The lumen traveling device is configured with one or more light emittingdiodes in sensor 4106 to induce autofluorescence of the lumen surface.The LED is configured to emit electromagnetic energy at a wavelength ofabout 340 nm. Ultraviolet LEDs constructed of quaternary AlGaInN onsmall area devices (<100 um diameter) and operating in the range of 340nm wavelength are described by Peng et al., in Applied Physics Letters,85:1436-1438, 2004, which is incorporated herein by reference.Autofluorescence emitted from an atherosclerotic plaque can bedistinguished from that of the normal luminal surface of thevasculature, using response control circuitry 4110. Autofluorescenceassociated with the lumen wall is detected at specific peak wavelengths,e.g., 395 nm and 450 nm, using a CMOS (complementary metal-oxidesemiconductor) imaging sensor in sensor 4106. Differences in theautofluorescence spectra are used to differentiate between normal,collagen thick and macrophage thick plaques. See, e.g., Marcu et al.,Atherosclerosis, 2005, 181:295-303, which is incorporated herein byreference.

Upon detection of an atherosclerotic plaque, the lumen traveling devicecan be instructed by response control circuitry 4110 to release atherapeutic agent, everolimus, which either stabilizes or causesregression of the plaque without catastrophic rupture. Everolimus[40-O-(2-hydroxyethyl)-rapamycin] is a rapamycin derivative thatinhibits the activity of mammalian target of rapamycin (mTOR) andselectively clears macrophages in vulnerable plaques without alteringthe viability of plaque-stabilizing smooth muscle cells. See, e.g.,Verheye, et al., J. Am. Coll. Cardiol., 2007, 49:706-715, which isincorporated herein by reference. The lumen traveling device can includea reservoir containing everolimus. Upon detection of an atheroscleroticplaque, the lumen traveling device is instructed to release theeverolimus in the immediate vicinity of the plaque. Alternative oradditional plaque stabilizing agents can be incorporated into reservoir4112 or additional reservoirs (not shown). Examples of additional plaquestabilizing agents include but are not limited to HMG-CoA-reductaseinhibitors (statins), angiotensin-converting enzyme (ACE) inhibitors,antihypertensive agents, beta-blocking agents, and antiplatelet agents.

As shown in FIG. 42, a method for detecting and treating atheroscleroticplaques in the vasculature of a mammalian subject can thus includeintroducing a lumen traveling device into the vasculature of a subjectat 4202; activating a propelling mechanism on the lumen traveling deviceto cause the lumen traveling device to travel through the vasculature ofthe subject at 4204; emitting a first wavelength of electromagneticradiation with a light emitting diode on the lumen traveling device at4206; detecting an atherosclerotic plaque in the vasculature of thesubject by sensing a second wavelength of electromagnetic radiation withan imaging sensor in the lumen traveling device, wherein the secondwavelength of electromagnetic radiation is emitted by theatherosclerotic plaque in response to the first wavelength ofelectromagnetic radiation at 4208; and releasing a therapeutic agentfrom a reservoir of the lumen traveling device in response to detectionof the atherosclerotic plaque at 4210.

FIG. 43, illustrates a block diagram of a system 4300 that includes aset of instructions 4304 for operating a lumen traveling device. Anembodiment of system 4300 is provided using non-transitory machinereadable media 4302 for use in a lumen traveling device control systemfor controlling a lumen traveling device including a light emittingdiode, an imaging sensor, a reservoir containing a therapeutic agent fortreatment of an atherosclerotic plaque, and a propelling mechanism.Non-transitory machine readable media 4302 including a set ofinstructions 4304, including one or more instructions that cause thelumen traveling device control system to activate the propellingmechanism to cause the lumen traveling device to travel through thevasculature of the subject; one or more instructions that cause thelumen traveling device control system to direct the light emitting diodeto emit a first wavelength of electromagnetic radiation; one or moreinstructions that cause the lumen traveling device control system todirect the detection of an atherosclerotic plaque by sensing a secondwavelength of electromagnetic radiation emitted by the atheroscleroticplaque with the imaging sensor; and one or more instructions that causethe lumen traveling device control system to release the therapeuticagent from the reservoir of the lumen traveling device in response todetection of an atherosclerotic plaque. The one or more instructions maybe, for example, computer executable and/or logic implementedinstructions. In an embodiment, the non-transitory machine readablemedia 4302 can include computer readable media 4306. In an embodiment,the non-transitory machine readable media 4302 can includerecordable-type media 4308.

Prophetic Example 2 Detecting and Treating Lung Cancer in the BronchialTree with a Lumen Traveling Device

A method for detecting and treating a cancerous lesion in the bronchialairways of a mammalian subject can be performed with a system includingat least one lumen traveling device configured to travel through thebronchial body tube tree up a concentration gradient of one or morecancer-associated analytes in the exhaled breath to reach the cancerouslesion and to controllably perform an action to treat the cancerouslesion. The vast majority of primary lung cancers are carcinomas of thelung, derived from bronchial epithelial cells lining the bronchialairways. The main types of lung cancer are small cell lung carcinoma andnon-small cell lung carcinoma. Small cell lung carcinoma tends to arisein the larger airways (e.g., primary and secondary bronchi), and growsrapidly. Non-small cell carcinoma includes squamous cell lung carcinoma(originating primarily near a central bronchus), adenocarcinoma(originating primarily in peripheral lung tissue), and large cellcarcinoma. The diagnosis of lung cancer often occurs at the first signsof symptoms (e.g., weight loss, coughing blood, difficulty breathing), apoint at which the cancer may have already spread extensively within thelung and possibly metastasized. As such, early diagnosis is critical toearly treatment and survival.

In this prophetic example, as depicted in FIG. 44, a lumen travelingdevice 4400 containing one or more sensors for sensing analytes such asvolatile organic compounds associated with lung cancer can be introducedinto the lungs 4404 of a subject. Lumen traveling device 4400 is used incombination with remote device 4412, which includes a portion of thecontrol circuitry used for controlling lumen traveling device 4400 andprovides power to lumen traveling device 4400. Data and power signalsare transmitted between remote device 4412 and lumen traveling device4400 as indicated by the dashed line. Lumen traveling device 4400 isintroduced into the bronchial body tube tree 4402 either through directinhalation or with a bronchoscope using methods similar to thosedescribed for placement of a tracheobronchial stent (see, e.g., Herth,et al., Chest, 2001, 119:1910-1912, which is incorporated herein byreference).

Lumen traveling device 4400 can travel through the bronchial body tubetree 4402 following the concentration gradient of one or more analytes,e.g., volatile organic compounds, sensed in the exhaled breath of asubject. The lumen traveling device 4400 includes sensor 4406 with anelectronic nose configured to sense one or more cancer-associatedanalytes 4408 (e.g., volatile organic compound) in the exhaled breath ofa subject, wheeled propelling mechanism 4409 (as depicted in FIG. 1),and an active portion (not shown in FIG. 44, but is an electromagneticenergy source of the type depicted in FIG. 6C). Lumen traveling device4400 also includes control circuitry, including response controlcircuitry, operating in cooperation with control circuitry on remotedevice 4412. A cancer-associated analyte 4408 originates from and is atits highest concentration at a cancerous lesion 4410 residing in thelumen of the bronchial body tube tree 4402. The sensor 4406 of the lumentraveling device 4400 can continuously sense the exhaled breath as itmoves through the bronchial body tube tree 4402. Response controlcircuitry on lumen traveling device 4400 can compare the concentrationof the cancer-associated analyte 4408 at a current location with thehighest concentration sensed so far. The lumen traveling device canselect a path of travel based on the concentration gradient of a sensedcancer-associated analyte 4408 and ultimately reaches the source of theanalyte, the cancerous lesion 4410. Upon reaching the source of thecancer-associated analyte 4408, the lumen traveling device can beinstructed to perform an action designed to eliminate the cancerouslesion 4410 by activating the electromagnetic energy source to emitelectromagnetic energy.

The lumen traveling device can be configured with one or more sensorsfor sensing one or more cancer-specific analytes in the bronchial treeof a subject. As an example, the one or more sensed cancer-specificparameters can be one or more analytes expired in the breath of thesubject. A number of analytes have been detected in the expired breathof cancer patients, examples of which include but are not limited to,volatile organic compounds (VOCs), interleukin 6 (IL-6), andendothelin-1 (see, e.g., Dweik & Amann, J. Breath Res., 2008; 030301 (3pp) and Phillips et al., Chest, 2003; 123:2115-2123, each of which isincorporated herein by reference). A number of specific volatile organiccompounds are elevated in the expired breath of subjects with cancer,including but not limited to butane, 3-methyl tridecane, 7-methyltridecane, 4-methyl octane, 3-methyl hexane, heptane, 2-methyl hexane,pentane, and 5-methyl decane. Sensor 4206 can sense one or more volatileorganic compounds in the exhaled breath of a subject. The sensor is aform of electronic nose capable of detecting volatile organic compoundsin exhaled breath (see, e.g., Machado et al., Am. J. Respir. Crit. CareMed., 2005; 171:1286-1291, which is incorporated herein by reference).The sensor can include one or more polymer composite sensors whichundergo a reversible change in electrical resistance when exposed to atarget vapor or analyte. The resistance change of each sensor is uniquebecause of the chemical diversity of the sensor materials. The patternof resistance changes obtained from the sensor array constitutes a“smellprint”. A particular smellprint is indicative of a pathologicalstate, e.g., cancer. Examples of micro and nanoscale electronic nosesare described in Rolfe, B., “Toward Nanometer-Scale Sensing Systems:Natural and Artificial Noses as Models for Ultra-Small, Ultra-DenseSensing Systems,” in Advances in Computers, Volume 71, ed. M Zelkowitz,Elsevier, B. V., 2007.

As shown in FIG. 45, the method of detecting and treating a lesion inthe bronchial airways of a subject using a lumen traveling device thusincludes introducing a lumen traveling device into the bronchial airwayof the subject at 4502; sensing a analyte produced by the lesion in theexhaled breath of the subject with a sensor including an electronic noseon the lumen traveling device, as the lumen traveling device movesthrough the bronchial airway with a propelling mechanism on the lumentraveling device at 4504; determining a concentration gradient of theanalyte with control circuitry on the lumen traveling device at 4506;moving the lumen traveling device through the bronchial airway along theconcentration gradient in the direction of the highest concentration ofthe analyte at 4508; moving along the concentration gradient until theconcentration gradient reverses direction at 4510; identifying thelocation of the lesion as the region of highest concentration of theanalyte, wherein the region of highest concentration is identified bythe change in direction of the concentration gradient at 4512; movingthe lumen traveling device to the location of the lesion as determinedby the change in direction of the concentration gradient at 4514; anddelivering a treatment to the lesion with the lumen traveling device at4516. Upon reaching the origin of a sensed cancer-associated analyte,the lumen traveling device is instructed by the control circuitry toperform a treatment action, specifically delivering electromagneticenergy to ablate the lesion.

In related embodiments, the lumen traveling device can release one ormore chemotherapeutic agent, such as cisplatin, etoposide, carboplatin,cyclophosphamide, doxorubicin, vincristine, gemcitabine, topotecan,instead of or in addition to electromagnetic energy to treat the lesion.

As shown in FIG. 46, instructions for performing the method can beprovided on non-transitory machine readable media as described elsewhereherein, which can be carried fully or in part on the lumen travelingdevice, or which can be provided on various other types of media. Anembodiment of system 4600 is provided using non-transitory machinereadable media 4602 including a set of instructions 4604 including oneor more instructions that cause the lumen traveling device controlsystem to direct a sensor including an electronic nose on a lumentraveling device to sense a analyte indicative of a lesion in abronchial airway of a subject while the lumen traveling device movesthrough the bronchial airway; one or more instructions that cause thelumen traveling device control system to determine a concentrationgradient of the analyte; one or more instructions that cause the lumentraveling device control system to direct at least one of a steeringmechanism and a propelling mechanism on the lumen traveling device tomove the lumen traveling device through the bronchial airway along theconcentration gradient in the direction of the highest concentration ofthe analyte with a propelling mechanism on the lumen traveling device;one or more instructions that cause the lumen traveling device controlsystem to detect when the concentration gradient reverses direction; oneor more instructions that cause the lumen traveling device controlsystem to reverse the direction of movement of the lumen travelingdevice when the concentration gradient changes direction; one or moreinstructions that cause the lumen traveling device control system todirect at least one of the steering mechanism and the propellingmechanism on the lumen traveling device to move the lumen travelingdevice to the location of the lesion as determined by the change indirection of the concentration gradient; and one or more instructionsthat cause the lumen traveling device control system to direct the lumentraveling device to deliver a treatment to the lesion. The one or moreinstructions may be, for example, computer executable and/or logicimplemented instructions. In an embodiment, the non-transitory machinereadable media 4602 can include computer readable media 4606. In anembodiment, the non-transitory machine readable media 4602 can includerecordable-type media 4608.

Prophetic Example 3 Detecting and Treating a Meningeal Malignancy in theCerebrospinal Fluid with a Lumen Traveling Device

In another prophetic example, a method is provided for detecting andtreating a meningeal malignancy in the central nervous system of amammalian subject. The method includes using at least one lumentraveling device configured to travel through the cerebrospinal fluid,sense one or more analyte associated with the meningeal malignancy, andcontrollably perform an action to treat the meningeal malignancy.Meningeal malignancy results from metastasis of intracranial orextracranial tumors to the leptomeninges (the arachnoid membrane and thepia mater). The cerebrospinal fluid (CSF) flows in the subarachnoidspace between the pia and the arachnoid and may provide a route formetastasis along the entire neuraxis. In many instances, thechemotherapeutic drugs used to treat extracranial tumors do not readilycross the blood brain barrier and as such the central nervous system canbecome a sanctuary for metastasizing tumor cells. Examples of tumorsthat can metastasize to the meninges include leukemia, lymphoma,melanoma, breast and lung carcinoma, Ewing's sarcoma, rhabdomyosarcoma,retinoblastoma, and brain tumors. Various manifestations of meningealmalignancy are referred to as carcinomatous meningitis, leptomeningealcancer, leptomeningeal carcinoma, leptomeningeal metastasis, meningealcarcinomatosis, and neoplastic meningitis.

The lumen traveling device can include one or more sensors for sensingparameters associated with meningeal malignancy in the flow route of theCSF, e.g., the subarachnoid space and the ventricles. Examples ofparameters associated with meningeal malignancy that can be measured inthe CSF include but are not limited to circulating tumor cells, elevatedprotein, reduced glucose and increase in specific biomarkers. See, e.g.,Pavlidis, Ann. Oncol., 2004, 15(Suppl 4):iv285-iv291, which isincorporated herein by reference. The gold standard for diagnosis ofmeningeal malignancy is the presence of circulating tumor cells in theCSF and as such, the one or more sensors associated with the lumentraveling device are configured to sense circulating tumor cells. Acirculating tumor cell derived from metastasis of a solid tumor will beconsiderably larger in volume than the limited number of blood cellsnormally found in the CSF and can be differentiated from other cellsbased on size using filtration and/or electrical impedance. Acirculating tumor cell can be as large as 2000 fL or 2.5 to 5 timeslarger than white blood cells the latter of which range in volume rangefrom 100 to 450 fL. Circulating tumor cells can be detected based onsize using electrical impedance. The lumen traveling device can beconfigured to include a microelectromechanical system (MEMS)miniaturized Coulter counter for differentiating cells based on volumeas described (see, e.g., Zheng et al., “Design and fabrication of amicro coulter counter with thin film electronics,” Proceedings of 2006International Conference on Microtechnologies in Medicine and Biology,IEEE, Okinawa, Japan, 9-12 May, 2006 and Gao et al., “A micro sensingprobe for detecting individual biological cells,” Proceedings of the25^(th) Annual International Conference of the IEEE EMBS, Cancun,Mexico, Sep. 17-21, 2003, each of which is incorporated herein byreference).

A method of detecting and treating meningeal malignancy can includeintraventricular placement of one or more lumen traveling devices intothe CSF flow route of a subject as illustrated in FIG. 47. As shown inFIG. 47, lumen traveling device 4702 can be introduced into the lateralventricle 4704 of subject 4700, from which it can travel through the CSFflow route. Lumen traveling device 4702 can be introduced into thelateral ventricle 4704 using a ventricular catheter 4706. The subject4700 can be given a local anesthetic at insertion site 4708. A hole canbe drilled in the skull 4710 at the insertion site 4708. The ventricularcatheter 4706 can be inserted through the skull 4710 at insertion site4708 and through the cerebral cortex 4712 to a depth of about sixcentimeters to reach the lateral ventricle 4704. The lumen travelingdevice 4702 can be released into the lateral ventricle 4704 from whichit may travel into other parts of the CSF flow route including the thirdventricle 4714 and the fourth ventricle 4716. Alternatively, the lumentraveling device 4702 can be placed in the CSF flow route by intrathecalinjection into the central canal of the spinal cord.

In response to sensing a circulating tumor cell and or a meningealmalignancy biomarker in the CSF, the lumen traveling device can beinstructed to release a chemotherapeutic agent from a reservoir on thelumen traveling device. Chemotherapeutic agents commonly used to treatmeningeal malignancy include but are not limited to methotrazate,cyarabine, thiotepa, diaziquone, 6-mercaptopurine, mafosfamide/4HC, ortopotecan.

As shown in FIG. 48, a method of detecting and treating a meningealmalignancy can thus include introducing a lumen traveling device into acerebrospinal fluid flow route of a subject at 4802 causing the lumentraveling device to travel through the cerebrospinal fluid flow route at4804; detecting circulating tumor cells from a meningeal malignancy witha microelectromechanical system miniaturized Coulter counter on thelumen traveling device, based upon differentiation of circulating tumorcells by volume at 4806; and in response to detection of circulatingtumor cells, releasing a chemotherapeutic agent from a reservoir on thelumen traveling device at 4808.

FIG. 49 illustrates a block diagram of a system 4900 that includesnon-transitory machine readable media 4902 including a set ofinstructions 4904 including: one or more instructions that cause thelumen traveling device control system to direct at least one of asteering mechanism and a propelling mechanism on the lumen travelingdevice to cause a lumen traveling device to travel through acerebrospinal fluid flow route of a subject; one or more instructionsthat cause the lumen traveling device control system to detectcirculating tumor cells from a meningeal malignancy with amicroelectromechanical system miniaturized Coulter counter on the lumentraveling device; and one or more instructions that cause the lumentraveling device control system to release a chemotherapeutic agent froma reservoir on the lumen traveling device in response to detectcirculating tumor cells with the microelectromechanical systemminiaturized Coulter counter on the lumen traveling device. The one ormore instructions may be, for example, computer executable and/or logicimplemented instructions. In an embodiment, the non-transitory machinereadable media 4902 can include computer readable media 4906. In anembodiment, the non-transitory machine readable media 4902 can includerecordable-type media 4908.

Prophetic Example 4 Detecting and Treating HIV Infection in the CentralNervous System Using a Lumen Traveling Device

A method for detecting and treating acquired immunodeficiency syndrome(AIDS) dementia complex in the central nervous system of a mammaliansubject can be implemented using at least one lumen traveling devicedesigned to travel through the cerebrospinal fluid, sense one or moreanalyte indicative of infection with human immunodeficiency virus (HIV),and controllably perform an action to treat the infection and or thedementia. AIDS dementia complex is a metabolic encephalopathy caused byHIV infection of brain macrophages and microglia and is a commonneurological disorder associated with AIDS. The infected cells secreteneurotoxins of both host and viral origin which cause disablingcognitive impairment accompanied by motor dysfunction, speech problemsand behavioral changes. In some individuals, the central nervous system(CNS) may be a reservoir for HIV with viral replication occurringrelatively independently from systemic infection. In addition, a numberof commonly used HIV drugs do not efficiently pass in to the CNS. See,e.g., Groothuis & Levy, J. Neurovirol., 1997, 3:387-400, which isincorporated herein by reference. AIDS dementia is confirmed in thoseHIV positive subjects experiencing cognitive impairment by testing thecerebrospinal fluid (CSF) for the presence of HIV antibodies or HIV RNA.A lumen traveling device can be configured to monitor the CSF of an HIVpositive subject for infection in the CNS and to directly administer oneor more drugs into the CSF.

A method for detecting and treating AIDS dementia complex in the CNS ofan HIV positive subject can include use of a lumen traveling device withone or more sensors configured to sense one or more markers of HIVinfection in the CNS. In this example, the sensors are configured todetect HIV antibodies in the CSF generated by the body's immune responseto HIV infection. The sensors are one or more carbon nanotube-fieldeffect transistors as described by Kim et al., Anal. Biochem., 2008,381:193-198, which is incorporated herein by reference. Carbon nanotubesare functionalized with all or part of the HIV surface glycoprotein 41(gp41) and are incorporated into one or more fluid contacting surfacesof the lumen traveling device. Binding of the target HIV antibodies inthe CSF to the gp41 fragments on the carbon nanotubes can be detected bymonitoring the gating effects induced by the charges associated with thebound HIV antibodies. A similar approach can be used to detect HIV RNAin which the carbon nanotubes are functionalized with an RNA bindingmoiety such as, for example, anti-sense RNA/DNA, an aptamer, or apeptide nucleic acid (PNA).

The lumen traveling device containing one or more sensors for sensingone or more markers of HIV infection can be placed into the CSF flowroute of a subject by intraventricular insertion as described in FIG.43. Ideally, the lumen traveling device is placed into one of thecerebral ventricles using a ventricular catheter. The subject can begiven a local anesthetic on the scalp at the site of insertion. Anincision can be made in the skin and the skull can be drilled to createa hole in the skull through which the catheter can pass. The cathetercan be inserted to a depth of about 6 centimeters to reach the lateralventricle and the lumen traveling device released into the ventricularspace.

In response to sensing HIV antibodies or HIV RNA in the CSF, the lumentraveling device can be instructed by the response control circuitry toperform an action. In this instance, the action performed is release ofone or more antiretroviral drugs for treatment of HIV infection. Thelumen traveling device can administer one or more antiviral drugsdirectly into the CSF. Examples of antiviral drugs commonly used fortreating HIV/AIDS include but are not limited nucleoside analog reversetranscriptase inhibitors (e.g., AZT, stavudine, didanosine, zalcitabin,almivudine, abacavir, emtricitabine), nucleotide analog reversetranscriptase inhibitors (e.g., tenofovir, adefovir), non-nucleosidereverse transcriptase inhibitors (e.g., efavirenz, nevirapine,delavirdine, etravirine), protease inhibitors (e.g., ritonavir,indinavir, nelfinavir, saquinavir, fosamprenavir, lopinavir, atazanavir,tipranavir, darunavir), integrase inhibitors (e.g., raltegravir), entryor fusion inhibitors (e.g., enfuvirtide, maraviroc). Optionally, thelumen traveling device controllably releases drugs used to treat thesymptoms of AIDS dementia. These include but are not limited toantidepressants (e.g., fluoxetine, sertraline, citalopram, duloxetine)to improve symptoms of depression and antipsychotics (e.g., haloperidol,chlorpromazine, flupenthixol, clozapine, aripiprazole) to improvesymptoms of severe agitation or aggression, hallucinations, ordelusions.

As shown in FIG. 50, a method for detecting and treating acquiredimmunodeficiency syndrome dementia complex in the central nervous systemof a subject thus can include introducing a lumen traveling device intoa cerebral ventricle of a subject at 5002; activating the propellingmechanism to propel the lumen traveling device through the ventricle at5004; detecting the binding of human immunodeficiency virus marker toone or more carbon nanotube-field effect transistors functionalized withan human immunodeficiency virus marker binding moiety on afluid-contacting surface of the lumen traveling device at 5006; and inresponse to detection of human immunodeficiency virus marker in thecerebrospinal fluid, releasing the one or more antiretroviral drugs froma reservoir in the lumen traveling device 5008; wherein the activating apropelling mechanism, detecting the binding of human immunodeficiencyvirus mark, and releasing the one or more antiretroviral drugs inresponse to detection of human immunodeficiency virus marker areperformed under the control of control circuitry on the lumen travelingdevice.

As shown in the block diagram of FIG. 51, an associated system 5100 caninclude non-transitory machine readable media 5102 including a set ofinstructions 5104 including one or more instructions that cause thelumen traveling device control system to activate a propelling mechanismon a lumen traveling device to propel the lumen traveling device througha cerebral ventricle of a subject, the cerebral ventricle containingcerebrospinal fluid; one or more instructions that cause the lumentraveling device control system to detect the binding of a diseasemarker to one or more carbon nanotube-field effect transistorsfunctionalized with a disease marker binding moiety on afluid-contacting surface of the lumen traveling device; and one or moreinstructions that cause the lumen traveling device control system torelease the one or more drugs from a reservoir in the lumen travelingdevice in response to detection of the disease marker in thecerebrospinal fluid. The one or more instructions may be, for example,computer executable and/or logic implemented instructions. In anembodiment, the non-transitory machine readable media 5102 can includecomputer readable media 1506. In an embodiment, the non-transitorymachine readable media 5102 can include recordable-type media 5108.

Examples of Alternative and Combined Functionality

With respect to the appended claims, the recited operations therein maygenerally be performed in any order. Also, although various operationalflows are presented in a sequence(s), it should be understood that thevarious operations may be performed in other orders than those which areillustrated, or may be performed concurrently. Examples of suchalternate orderings may include overlapping, interleaved, interrupted,reordered, incremental, preparatory, supplemental, simultaneous,reverse, or other variant orderings, unless context dictates otherwise.Furthermore, terms like “responsive to,” “related to,” or otherpast-tense adjectives are generally not intended to exclude suchvariants, unless context dictates otherwise.

One skilled in the art will recognize that the herein describedcomponents (e.g., operations), devices, objects, and the discussionaccompanying them are used as examples for the sake of conceptualclarity and that various configuration modifications are contemplated.Consequently, as used herein, the specific exemplars set forth and theaccompanying discussion are intended to be representative of their moregeneral classes. In general, use of any specific exemplar is intended tobe representative of its class, and the non-inclusion of specificcomponents (e.g., operations), devices, and objects should not be takenlimiting. Different numbers and combinations of components andoperations disclosed herein can be used in different embodiments. It iscontemplated that more than one instance of a particular component oroperation can be included in an embodiment, and the different exemplarsof such components or operations presented herein are not consideredmutually exclusive unless context clearly dictates that this is thecase. For example, a lumen traveling device can include severalinstances of an “active portion,” and these instances can be the same,or different—e.g., a sample collector, a material release structure(e.g. for releasing a medication or drug), and a heating element.Different instances of a particular component or operation can operateindependently or in cooperation. As further examples, a lumen travelingdevice can include several instances of propelling mechanisms, e.g., itcan include both appendages and a paddle; a lumen traveling device canperform multiple operations relating to selecting a direction of travel,e.g. selecting a direction of travel based on determining whether aparticular direction has been previously travelled and determiningwhether a certain concentration of an analyte is sensed from thedirection of travel.

FIGS. 52-71 provide examples of methods and corresponding systems thatincluding various combinations of steps that can be performed with lumentraveling devices as described herein.

FIG. 52 is a flow diagram of a method 5200 of operating a lumentraveling device in a lumen of a body tube tree including activating apropelling mechanism on the lumen traveling device to propel the lumentraveling device within a body tube tree at 2202, determining a timebased on a signal from a timing device at 2204, and performing at leastone action with an active portion of the lumen traveling device based atleast in part upon the determined time at 2206, as in the method shownin FIG. 22, and further including detecting an arrival of the lumentraveling device at a branch point in the body tube tree with at leastone arrival sensor on the lumen traveling device, the branch pointincluding at least two branch channels at 5208; causing the propellingmechanism to move the lumen traveling device into one of the at leasttwo branch channels at 5210, storing information regarding at least oneof the at least two branch channels at 5212, sensing a positionindicator signal at 5214, sensing a local parameter value with aparameter sensor on the lumen traveling device at 5216 and performingthe at least one action with the active portion of the lumen travelingdevice based at least in part upon the determined time and at least inpart upon at least one of the local parameter value and the positionindicator signal at 5218.

FIG. 53 illustrates a block diagram of a system 5300 that is a variantof the system depicted in FIG. 21. System 5300 includes non-transitorymachine readable media 5302, including instructions 2104 as shown inFIG. 21 and further instructions 5304, including: one or moreinstructions that cause the lumen traveling device control system todetect an arrival of the lumen traveling device at a branch point in thebody tube tree with at least one arrival sensor on the lumen travelingdevice, the branch point including at least two branch channels; one ormore instructions that cause the lumen traveling device control systemto direct the propelling mechanism on the lumen traveling device to movethe lumen traveling device into one of the at least two branch channels;one or more instructions that cause the lumen traveling device controlsystem to store information regarding at least one of the at least twobranch channels; one or more instructions that cause the lumen travelingdevice control system to direct the sensing of a position indicatorsignal; one or more instructions that cause the lumen traveling devicecontrol system to direct the sensing of a local parameter value with aparameter sensor on the lumen traveling device; and one or moreinstructions that cause the lumen traveling device control system todirect the active portion of the lumen traveling device to perform theaction based at least in part upon at least one of the local parametervalue and the position indicator signal. The one or more instructionsmay be, for example, computer executable and/or logic implementedinstructions. In an embodiment, the non-transitory machine readablemedia 5302 can include computer readable media 5306. In an embodiment,the non-transitory machine readable media 5302 can includerecordable-type media 5308.

FIG. 54 is a flow diagram of a method 5400 of operating a lumentraveling device, which is an expansion of the method of FIG. 34,including obtaining a map of at least a portion of a body tube treeincluding a plurality of branched, interconnected channels at 3402,determining a current location of a lumen traveling device on the mapwith an operation performed on-board the lumen traveling device, thelumen traveling device located within the body tube tree represented bythe map at 3404, determining a target location for the lumen travelingdevice within the body tube tree at 3406, planning a path of travel forthe lumen traveling device, the planned path of travel leading at leasta portion of the way between the current location and the targetlocation at 3408, and causing movement of the lumen traveling devicethrough the body tube tree along the path of travel at 3410 causingmovement of the lumen traveling device through the body tube tree alongthe path of travel, as in FIG. 34, and further including activating apropelling mechanism on the lumen traveling device to propel the lumentraveling device through the body tube tree along the path of travel at5412, detecting an arrival of the lumen traveling device at a branchpoint in the body tube tree with at least one arrival sensor on thelumen traveling device, the branch point including at least two branchchannels at 5414, selecting at least one of the at least two branchchannels at 5416, activating the propelling mechanism to propel thelumen traveling device into the selected branch channel at 5418, storinginformation regarding at least one of the at least two branch channelsat 5420, determining a time based on a signal from a timing device at5422, sensing a local parameter value with a parameter sensor on thelumen traveling device at 5424, and performing an action with the activeportion of the lumen traveling device based at least in part upon atleast one of the local parameter value and the determined time at 5426.

FIG. 55 illustrates a block diagram of a system 5500 that is a variantof system 3300 depicted in FIG. 33. System 5500 is provided usingnon-transitory machine readable media 5502, and includes a set ofinstructions 3304, as shown in FIG. 33, including one or moreinstructions that cause the lumen traveling device control system toobtain a map of at least a portion of a body tube tree including aplurality of branched, interconnected channels; one or more instructionsthat cause the lumen traveling device control system to determine acurrent location of a lumen traveling device on the map with anoperation performed on-board the lumen traveling device, the lumentraveling device located within the body tube tree represented by themap; one or more instructions that cause the lumen traveling devicecontrol system to determine a target location for the lumen travelingdevice within the body tube tree; one or more instructions that causethe lumen traveling device control system to determine a path of travelfor the lumen traveling device, the path of travel leading at least aportion of the way between the current location and the target location;and one or more instructions that cause the lumen traveling devicecontrol system to direct at least one of a steering mechanism and apropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree along the path oftravel. Non-transitory machine readable media 5502 further includes aset of instructions 5504, including one or more instructions that causethe lumen traveling device control system to detect an arrival of thelumen traveling device at a branch point in the body tube tree with atleast one arrival sensor on the lumen traveling device, the branch pointincluding at least two branch channels; one or more instructions thatcause the lumen traveling device control system to select at least oneof the at least two branch channels; one or more instructions that causethe lumen traveling device control system to activate the propellingmechanism to propel the lumen traveling device into the selected branchchannel; one or more instructions that cause the lumen traveling devicecontrol system to store information regarding at least one of the atleast two branch channels; one or more instructions that cause the lumentraveling device control system to determine a time based on a signalfrom a timing device; one or more instructions that cause the lumentraveling device control system to direct the sensing of a localparameter value with a parameter sensor on the lumen traveling device;and one or more instructions that cause the lumen traveling devicecontrol system to direct the active portion of the lumen travelingdevice to perform an action based at least in part upon at least one ofthe local parameter value and the determined time. In an embodiment, thenon-transitory machine readable media 5502 can include computer readablemedia 5506. In an embodiment, the non-transitory machine readable media5502 can include recordable-type media 5508.

FIG. 56 is a flow diagram of a method 5600 of operating a lumentraveling device, based on the method shown in FIG. 22, and similarlyincluding activating a propelling mechanism on the lumen travelingdevice to propel the lumen traveling device within a body tube tree at2202, determining a time based on a signal from a timing device at 2204,and performing at least one action with an active portion of the lumentraveling device based at least in part upon the determined time at2206. The method further includes determining a current location of alumen traveling device on a map of at least a portion of a body tubetree including a plurality of branched, interconnected channels with anoperation performed on-board the lumen traveling device, the lumentraveling device located within the body tube tree represented by themap at 5608, determining a target location for the lumen travelingdevice within the body tube tree at 5610, planning a path of travel forthe lumen traveling device, the path of travel leading at least aportion of the way between the current location and the target locationat 5612, causing movement of the lumen traveling device through the bodytube tree along the path of travel at 5614, detecting an arrival of thelumen traveling device at a branch point in the body tube tree with atleast one arrival sensor on the lumen traveling device, the branch pointincluding at least two branch channels at 5616, selecting one of the atleast two branch channels at 5618, and directing the lumen travelingdevice into the selected branch channel at 5620.

FIG. 57 illustrates a block diagram of a system 5700 that is a variantof the system shown in FIG. 21. System 5700 is provided usingnon-transitory machine readable media 5702, and includes a set ofinstructions 2104 for operating a lumen traveling device, as shown inFIG. 21, including one or more instructions that cause the lumentraveling device control system to activate a propelling mechanism on alumen traveling device to propel the lumen traveling device within abody tube tree; one or more instructions that cause the lumen travelingdevice control system to determine a time based on a signal from atiming device; and one or more instructions that cause the lumentraveling device control system to direct the active portion of thelumen traveling device to perform at least one action based at least inpart upon the determined time. 5700 further includes a set ofinstructions 5704, including one or more instructions that cause thelumen traveling device control system to determine a current location ofa lumen traveling device on a map of at least a portion of a body tubetree including a plurality of branched, interconnected channels with anoperation performed on-board the lumen traveling device, the lumentraveling device located within the body tube tree represented by themap; one or more instructions that cause the lumen traveling devicecontrol system to determine a target location for the lumen travelingdevice within the body tube tree; one or more instructions that causethe lumen traveling device control system to plan a path of travel forthe lumen traveling device, the path of travel leading at least aportion of the way between the current location and the target location;one or more instructions that cause the lumen traveling device controlsystem to detect an arrival of the lumen traveling device at a branchpoint in the body tube tree with at least one arrival sensor on thelumen traveling device, the branch point including at least two branchchannels; one or more instructions that cause the lumen traveling devicecontrol system to select one of the at least two branch channels; one ormore instructions that cause the lumen traveling device control systemto direct at least one of a steering mechanism on the lumen travelingdevice and the propelling mechanism to cause the lumen traveling deviceto move into the selected branch channel. The one or more instructionsmay be, for example, computer executable and/or logic implementedinstructions. In an embodiment, the non-transitory machine readablemedia 5702 can include computer readable media 5706. In an embodiment,the non-transitory machine readable media 5702 can includerecordable-type media 5708.

FIG. 58 is a flow diagram of a method 5800 of operating a lumentraveling device, which is a variant of the method of FIG. 28, andincludes identifying at least two possible directions of travel of alumen traveling device through a body tube tree, the body tube treeincluding a plurality of branched, interconnected channels, and the atleast two possible directions of travel corresponding to at least two ofthe branched, interconnected channels at 2802; receiving datarepresenting at least one parameter value sensed from at least one ofthe at least two possible directions of travel of the lumen travelingdevice through the body tube tree at 2804; selecting a direction oftravel from the at least two directions of travel based at least in parton the data representing at least one parameter value sensed from atleast one of the at least two possible directions of travel of the lumentraveling device through the body tube tree at 2806; and directing atleast one of the steering mechanism and the propelling mechanism on thelumen traveling device to cause the lumen traveling device to movethrough the body tube tree in the selected direction of travel at 2808.The method further includes receiving information related to whether ornot at least one of at least two possible directions of travel of thelumen traveling device through the body tube tree has previously beentraveled by the lumen traveling device at 5810 and selecting thedirection of travel from the at least two possible directions of travelbased at least in part on the information related to whether or not atleast one of at least two possible directions of travel of the lumentraveling device through the body tube tree has previously been traveledby the lumen traveling device at 5812.

FIG. 59 illustrates a block diagram of a system 5900 that is a variantof the system shown in FIG. 27. An embodiment of system 5900 is providedusing non-transitory machine readable media 5902 including a set ofinstructions 2704, including one or more instructions that cause thelumen traveling device control system to identify at least two possibledirections of travel of a lumen traveling device through a body tubetree, the body tube tree including a plurality of branched,interconnected channels, and the at least two possible directions oftravel corresponding to at least two of the branched, interconnectedchannels; one or more instructions that cause the lumen traveling devicecontrol system to receive data representing at least one parameter valuesensed from at least one of the at least two possible directions oftravel of the lumen traveling device through the body tube tree; one ormore instructions that cause the lumen traveling device control systemto select a direction of travel from the at least two directions oftravel based at least in part on the data representing at least oneparameter value sensed from at least one of the at least two possibledirections of travel of the lumen traveling device through the body tubetree; and one or more instructions that cause the lumen traveling devicecontrol system to direct at least one of the steering mechanism and thepropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree in the selecteddirection of travel. Non-transitory machine readable media 5902 furtherincludes instructions 5904, including one or more instructions thatcause the lumen traveling device control system to receive informationrelated to whether or not at least one of at least two possibledirections of travel of the lumen traveling device through the body tubetree has previously been traveled by the lumen traveling device; and oneor more instructions that cause the lumen traveling device controlsystem to select a direction of travel from the at least two possibledirections of travel based at least in part on the information relatedto whether or not at least one of at least two possible directions oftravel of the lumen traveling device through the body tube tree haspreviously been traveled by the lumen traveling device. The one or moreinstructions may be, for example, computer executable and/or logicimplemented instructions. In an embodiment, the non-transitory machinereadable media 5902 can include computer readable media 5906. In anembodiment, the non-transitory machine readable media 5902 can includerecordable-type media 5908.

FIG. 60 is a flow diagram of a method 6000 of operating a lumentraveling device that is a variant of the method of FIG. 30, andincludes identifying at least two possible directions of travel of alumen traveling device through a body tube tree, the body tube treeincluding a plurality of branched, interconnected channels, and the atleast two possible directions of travel corresponding to at least two ofthe branched, interconnected channels at 3002; receiving datarepresenting a stored parameter value relating to a previous event at3004; selecting a direction of travel from the at least two directionsof travel based at least in part on the data representing a storedparameter value relating to a previous event at 3006; and directing atleast one of a steering mechanism and a propelling mechanism on thelumen traveling device to cause the lumen traveling device to movethrough the body tube tree in the selected direction of travel at 3008.The method further includes receiving information related to whether ornot at least one of at least two possible directions of travel of thelumen traveling device through the body tube tree has previously beentraveled by the lumen traveling device at 6010, and selecting thedirection of travel from the at least two possible directions of travelbased at least in part on the information related to whether or not atleast one of at least two possible directions of travel of the lumentraveling device through the body tube tree has previously been traveledby the lumen traveling device at 6012.

FIG. 61 illustrates a block diagram of a system 6100 that is a variantof the system depicted in FIG. 29 and includes a non-transitory machinereadable media 6102 bearing instructions for operating a lumen travelingdevice. Non-transitory machine readable media 6102 includes a set ofinstructions 2904 including one or more instructions that cause thelumen traveling device control system to identify at least two possibledirections of travel of a lumen traveling device through a body tubetree, the body tube tree including a plurality of branched,interconnected channels, and the at least two possible directions oftravel corresponding to at least two of the branched, interconnectedchannels; one or more instructions that cause the lumen traveling devicecontrol system to receive data representing a stored parameter valuerelating to a previous event associated with at least one of the atleast two possible directions of travel; one or more instructions thatcause the lumen traveling device control system to select a direction oftravel from the at least two directions of travel based at least in parton the data representing a stored parameter value relating to a previousevent associated with at least one of the at least two possibledirections of travel; and one or more instructions that cause the lumentraveling device control system to direct at least one of a steeringmechanism and a propelling mechanism on the lumen traveling device tocause the lumen traveling device to move through the body tube tree inthe selected direction of travel. Non-transitory machine readable media6102 further includes set of instruction 6104 including one or moreinstructions that cause the lumen traveling device control system toreceive information related to whether or not at least one of at leasttwo possible directions of travel of the lumen traveling device throughthe body tube tree has previously been traveled by the lumen travelingdevice; and one or more instructions that cause the lumen travelingdevice control system to select a direction of travel from the at leasttwo possible directions of travel based at least in part on theinformation related to whether or not at least one of at least twopossible directions of travel of the lumen traveling device through thebody tube tree has previously been traveled by the lumen travelingdevice. The one or more instructions may be, for example, computerexecutable and/or logic implemented instructions. In an embodiment, thenon-transitory machine readable media 6102 can include computer readablemedia 6106. In an embodiment, the non-transitory machine readable media6102 can include recordable-type media 6108.

FIG. 62 is a flow diagram of a method 6200 of operating a lumentraveling device, that is a variant of the method of FIG. 34, andincludes obtaining a map of at least a portion of a body tube treeincluding a plurality of branched, interconnected channels at 3402;determining a current location of a lumen traveling device on the mapwith an operation performed on-board the lumen traveling device, thelumen traveling device located within the body tube tree represented bythe map at 3404; determining a target location for the lumen travelingdevice within the body tube tree at 3406; planning a path of travel forthe lumen traveling device, the planned path of travel leading at leasta portion of the way between the current location and the targetlocation at 3408; and causing movement of the lumen traveling devicethrough the body tube tree along the path of travel at 3410. The methodfurther includes identifying at least two possible directions of travelof a lumen traveling device through the body tube tree at 6212,receiving information related to whether or not at least one of at leasttwo possible directions of travel of the lumen traveling device throughthe body tube tree has previously been traveled by the lumen travelingdevice at 6214, selecting a direction of travel from the at least twopossible directions of travel based at least in part on the informationrelated to whether or not at least one of at least two possibledirections of travel of the lumen traveling device through the body tubetree has previously been traveled by the lumen traveling device, whereinthe selected direction of travel is expected to lie along the plannedpath of travel at 6216, and directing at least one of a steeringmechanism and a propelling mechanism on the lumen traveling device tocause the lumen traveling device to move through the body tube tree inthe selected direction of travel at 6218.

FIG. 63 illustrates a block diagram of a system 6300 that includesnon-transitory machine readable media 6302 bearing instructions foroperating a lumen traveling device. System 6300 is a variant of thesystem shown in FIG. 33. Non-transitory machine readable media 6302including a set of instructions 3304 including one or more instructionsthat cause the lumen traveling device control system to obtain a map ofat least a portion of a body tube tree including a plurality ofbranched, interconnected channels; one or more instructions that causethe lumen traveling device control system to determine a currentlocation of a lumen traveling device on the map with an operationperformed on-board the lumen traveling device, the lumen travelingdevice located within the body tube tree represented by the map; one ormore instructions that cause the lumen traveling device control systemto determine a target location for the lumen traveling device within thebody tube tree; one or more instructions that cause the lumen travelingdevice control system to plan a path of travel for the lumen travelingdevice, the path of travel leading at least a portion of the way betweenthe current location and the target location; and one or moreinstructions that cause the lumen traveling device control system todirect at least one of a steering mechanism and a propelling mechanismon the lumen traveling device to cause the lumen traveling device tomove through the body tube tree along the path of travel. Non-transitorymachine readable media 6302 further includes set of instructions 6304including one or more instructions that cause the lumen traveling devicecontrol system to identify at least two possible directions of travel ofa lumen traveling device through a body tube tree, the body tube treeincluding a plurality of branched, interconnected channels, and the atleast two possible directions of travel corresponding to at least two ofthe branched, interconnected channels; one or more instructions thatcause the lumen traveling device control system to receive informationrelated to whether or not at least one of at least two possibledirections of travel of the lumen traveling device through the body tubetree has previously been traveled by the lumen traveling device; one ormore instructions that cause the lumen traveling device control systemto select a direction of travel from the at least two possibledirections of travel based at least in part on the information relatedto whether or not at least one of at least two possible directions oftravel of the lumen traveling device through the body tube tree haspreviously been traveled by the lumen traveling device, wherein theselected direction of travel is expected to lie along the planned pathof travel; and one or more instructions that cause the lumen travelingdevice control system to direct at least one of a steering mechanism anda propelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree in the selecteddirection of travel. The one or more instructions may be, for example,computer executable and/or logic implemented instructions. In anembodiment, the non-transitory machine readable media 6302 can includecomputer readable media 6306. In an embodiment, the non-transitorymachine readable media 6302 can include recordable-type media 6308.

FIG. 64 is a flow diagram of a method 6400 of operating a lumentraveling device, that is a variant of the method shown in FIG. 40, andincludes obtaining a map of at least a portion of a body tube treeincluding a plurality of branched, interconnected channels at 3402;determining a current location of a lumen traveling device on the mapwith an operation performed on-board the lumen traveling device, thelumen traveling device located within the body tube tree represented bythe map at 3404; determining a target location for the lumen travelingdevice within the body tube tree at 3406; planning a path of travel forthe lumen traveling device, the planned path of travel leading at leasta portion of the way between the current location and the targetlocation at 3408; and causing movement of the lumen traveling devicethrough the body tube tree along the path of travel at 3410, where it isfurther specified at 4008 wherein planning the path of travel for thelumen traveling device includes planning a first path of travel leadingbetween the current location and an intermediate location and a planninga second path of travel leading between the intermediate location andthe target location and wherein causing movement of the lumen travelingdevice through the body tube tree along the path of travel includescausing the lumen traveling device to move along the first path oftravel leading between the current location and an intermediate locationand causing the lumen traveling device to move along the second path oftravel leading between the intermediate location and the targetlocation. In addition, it is further specified at 6412 wherein planningthe path of travel for the lumen traveling device includes planning afirst path of travel leading between the current location and anintermediate location and a planning a second path of travel leadingbetween the intermediate location and the target location and whereincausing movement of the lumen traveling device through the body tubetree along the path of travel includes causing the lumen travelingdevice to move along the first path of travel leading between thecurrent location and an intermediate location and causing the lumentraveling device to move along the second path of travel leading betweenthe intermediate location and the target location.

FIG. 65 illustrates a block diagram of a system 6500 that includes anon-transitory machine readable media 6502 including a set ofinstructions 3304, as shown in FIG. 33, wherein it is specified whereinthe one or more instructions that cause the lumen traveling devicecontrol system to plan a path of travel for the lumen traveling deviceinclude one or more instructions that cause the lumen traveling devicecontrol system to determine a first path of travel leading between thecurrent location and an intermediate location; and one or moreinstructions that cause the lumen traveling device control system todetermine a second path of travel leading between the intermediatelocation and the target location, at 3904, as in the system of FIG. 39.It is further specified wherein the one or more instructions that causethe lumen traveling device control system determine the first path oftravel include: one or more instructions that cause the lumen travelingdevice control system to identify at least two possible directions oftravel of the lumen traveling device through the body tube tree; one ormore instructions that cause the lumen traveling device control systemto receive information related to whether or not at least one of atleast two possible directions of travel of the lumen traveling devicethrough the body tube tree has previously been traveled by the lumentraveling device; and one or more instructions that cause the lumentraveling device control system to select a direction of travel from theat least two possible directions of travel based at least in part on theinformation related to whether or not at least one of at least twopossible directions of travel of the lumen traveling device through thebody tube tree has previously been traveled by the lumen travelingdevice, wherein the selected direction of travel is along the firstpath, as shown at 6504. The one or more instructions may be, forexample, computer executable and/or logic implemented instructions. Inan embodiment, the non-transitory machine readable media 6502 caninclude computer readable media 6506. In an embodiment, thenon-transitory machine readable media 6502 can include recordable-typemedia 6508.

FIG. 66 is a flow diagram of a method 6600 of operating a lumentraveling device, which is a variant of the method shown in FIG. 34.Method 6600 includes obtaining a map of at least a portion of a bodytube tree including a plurality of branched, interconnected channels at3402; determining a current location of a lumen traveling device on themap with an operation performed on-board the lumen traveling device, thelumen traveling device located within the body tube tree represented bythe map at 3404; determining a target location for the lumen travelingdevice within the body tube tree at 3406; planning a path of travel forthe lumen traveling device, the planned path of travel leading at leasta portion of the way between the current location and the targetlocation at 3408; and causing movement of the lumen traveling devicethrough the body tube tree along the path of travel at 3410. Method 6600further includes identifying at least two possible directions of travelof a lumen traveling device through a body tube tree at 6612; receivinginformation related to whether or not at least one of at least twopossible directions of travel of the lumen traveling device through thebody tube tree has previously been traveled by the lumen travelingdevice at 6614; receiving data representing at least one parameter valuesensed from at least one of the at least two possible directions oftravel of the lumen traveling device through the body tube tree at 6616;selecting a direction of travel from the at least two possibledirections of travel based at least in part on the data representing atleast one parameter value and at least in part on the informationrelated to whether or not at least one of at least two possibledirections of travel of the lumen traveling device through the body tubetree has previously been traveled by the lumen traveling device at 6618;and directing at least one of a steering mechanism and a propellingmechanism on the lumen traveling device to cause the lumen travelingdevice to move through the body tube tree in the selected direction oftravel at 6620. This method can be performed, for example, with a deviceas depicted in and described in connection with FIGS. 1, 2, 7 and 8.

FIG. 67 illustrates a block diagram of a system 6700 that includesnon-transitory machine readable media 6702 including instruction for usein a lumen traveling device control system. Non-transitory machinereadable media 6702 includes a set of instructions 3304, as shown inFIG. 33, for operating a lumen traveling device, including one or moreinstructions that cause the lumen traveling device control system toobtain a map of at least a portion of a body tube tree including aplurality of branched, interconnected channels; one or more instructionsthat cause the lumen traveling device control system to determine acurrent location of a lumen traveling device on the map with anoperation performed on-board the lumen traveling device, the lumentraveling device located within the body tube tree represented by themap; one or more instructions that cause the lumen traveling devicecontrol system to determine a target location for the lumen travelingdevice within the body tube tree; one or more instructions that causethe lumen traveling device control system to plan a path of travel forthe lumen traveling device, the path of travel leading at least aportion of the way between the current location and the target location;and one or more instructions that cause the lumen traveling devicecontrol system to direct at least one of a steering mechanism and apropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree along the path oftravel. Non-transitory machine readable media 6702 further includes oneor more instructions that cause the lumen traveling device controlsystem to identify at least two possible directions of travel of a lumentraveling device through a body tube tree; one or more instructions thatcause the lumen traveling device control system to receive informationrelated to whether or not at least one of at least two possibledirections of travel of the lumen traveling device through the body tubetree has previously been traveled by the lumen traveling device; one ormore instructions that cause the lumen traveling device control systemto receive data representing at least one parameter value sensed from atleast one of the at least two possible directions of travel of the lumentraveling device through the body tube tree; one or more instructionsthat cause the lumen traveling device control system to select adirection of travel from the at least two possible directions of travelbased at least in part on the data representing at least one parametervalue and at least in part on the information related to whether or notat least one of at least two possible directions of travel of the lumentraveling device through the body tube tree has previously been traveledby the lumen traveling device; and one or more instructions that causethe lumen traveling device control system to direct at least one of thesteering mechanism and the propelling mechanism on the lumen travelingdevice to cause the lumen traveling device to move through the body tubetree in the selected direction of travel, shown at 6704. The one or moreinstructions may be, for example, computer executable and/or logicimplemented instructions. In an embodiment, the non-transitory machinereadable media 6702 can include computer readable media 6706. In anembodiment, the non-transitory machine readable media 6702 can includerecordable-type media 6708.

FIG. 68 illustrates a block diagram of a system 6800 that includesnon-transitory machine readable media 6802. Non-transitory machinereadable media 6802 includes a set of instructions 3304 including one ormore instructions that cause the lumen traveling device control systemto obtain a map of at least a portion of a body tube tree including aplurality of branched, interconnected channels; one or more instructionsthat cause the lumen traveling device control system to determine acurrent location of a lumen traveling device on the map with anoperation performed on-board the lumen traveling device, the lumentraveling device located within the body tube tree represented by themap; one or more instructions that cause the lumen traveling devicecontrol system to determine a target location for the lumen travelingdevice within the body tube tree; one or more instructions that causethe lumen traveling device control system to plan a path of travel forthe lumen traveling device, the path of travel leading at least aportion of the way between the current location and the target location;and one or more instructions that cause the lumen traveling devicecontrol system to direct at least one of a steering mechanism and apropelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree along the path oftravel, wherein as indicated at 3904, the one or more instructions thatcause the lumen traveling device control system to plan a path of travelfor the lumen traveling device include: one or more instructions thatcause the lumen traveling device control system to determine a firstpath of travel leading between the current location and an intermediatelocation; and one or more instructions that cause the lumen travelingdevice control system to determine a second path of travel leadingbetween the intermediate location and the target location.Non-transitory machine readable media 6802 further includes set ofinstructions 6804 including wherein the non-transitory machine readablemedia includes: one or more instructions that cause the lumen travelingdevice control system to identify at least two possible directions oftravel of a lumen traveling device through the body tube tree; one ormore instructions that cause the lumen traveling device control systemto receive information related to whether or not at least one of atleast two possible directions of travel of the lumen traveling devicethrough the body tube tree has previously been traveled by the lumentraveling device; one or more instructions that cause the lumentraveling device control system to receive data representing at leastone parameter value sensed from at least one of the at least twopossible directions of travel of the lumen traveling device through thebody tube tree; one or more instructions that cause the lumen travelingdevice control system to select a direction of travel from the at leasttwo possible directions of travel based at least in part on the datarepresenting at least one parameter value sensed from at least one ofthe at least two possible directions of travel of the lumen travelingdevice through the body tube tree and at least in part on theinformation related to whether or not at least one of at least twopossible directions of travel of the lumen traveling device through thebody tube tree has previously been traveled by the lumen travelingdevice; and one or more instructions that cause the lumen travelingdevice control system to direct at least one of a steering mechanism anda propelling mechanism on the lumen traveling device to cause the lumentraveling device to move through the body tube tree in the selecteddirection of travel. The one or more instructions may be, for example,computer executable and/or logic implemented instructions. In anembodiment, the non-transitory machine readable media 6802 can includecomputer readable media 6806. In an embodiment, the non-transitorymachine readable media 6802 can include recordable-type media 6808.

FIG. 69 is a flow diagram of a method 6900 that is a variant of themethod shown in FIG. 32. Method 6900 includes receiving data includingat least one target parameter value representing a target locationtoward which the lumen traveling device is to travel through a body tubetree including a plurality of branched, interconnected channels, thetarget location being located within the body tube tree at 3202; sensingat least one parameter value representative of a current location of thelumen traveling device at 3204; determining whether the current locationof the lumen traveling device is the target location at 3206; directingan active portion of the lumen traveling device to perform an action ifthe current location is the target location at 3208; or directing atleast one of a steering mechanism and a propelling mechanism on thelumen traveling device to cause the lumen traveling device to movethrough the body tube tree in a selected direction of travel if thecurrent location is not the target location at 3210. The method furtherincludes determining the current location of the lumen traveling deviceon a map of at least a portion of a body tube tree, the lumen travelingdevice located within the body tube tree represented by the map at 6912;and planning a path of travel for the lumen traveling device, the pathof travel leading at least a portion of the way between the currentlocation and the target location, wherein directing at least one of asteering mechanism and a propelling mechanism on the lumen travelingdevice to cause the lumen traveling device to move through the body tubetree in a selected direction of travel if the current location is notthe target location along the planned path of travel at 6914.

FIG. 70 illustrates a block diagram of a system 7000 that includesnon-transitory machine readable media 7002. System 7000 is a variant ofthe system shown in FIG. 31. Non-transitory machine readable media 7002includes a set of instructions 3104 including one or more instructionsthat cause the lumen traveling device control system to receive dataincluding at least one target parameter value representing a targetlocation in a body tube tree, the body tube tree including a pluralityof branched, interconnected channels, the target location being locatedwithin the body tube tree; one or more instructions that cause the lumentraveling device control system to direct the sensing of at least oneparameter value representative of a current location of the lumentraveling device within the body tube tree; one or more instructionsthat cause the lumen traveling device control system to determinewhether the current location of the lumen traveling device is the targetlocation; one or more instructions that cause the lumen traveling devicecontrol system to direct an active portion of the lumen traveling deviceto perform an action if the current location is the target location; andone or more instructions that cause the lumen traveling device controlsystem to direct at least one of a steering mechanism and a propellingmechanism on the lumen traveling device to cause the lumen travelingdevice to move through the body tube tree in a selected direction oftravel if the current location is not the target location.Non-transitory machine readable media 7002 further includes set ofinstructions 7004 including one or more instructions that cause thelumen traveling device control system to receive data including at leastone target parameter value representing a target location in a body tubetree, the body tube tree including a plurality of branched,interconnected channels, the target location being located within thebody tube tree; one or more instructions that cause the lumen travelingdevice control system to direct the sensing of at least one parametervalue representative of a current location of the lumen traveling devicewithin the body tube tree; one or more instructions that cause the lumentraveling device control system to determine whether the currentlocation of the lumen traveling device is the target location; one ormore instructions that cause the lumen traveling device control systemto direct an active portion of the lumen traveling device to perform anaction if the current location is the target location; and one or moreinstructions that cause the lumen traveling device control system todirect at least one of a steering mechanism and a propelling mechanismon the lumen traveling device to cause the lumen traveling device tomove through the body tube tree in a selected direction of travel if thecurrent location is not the target location. The one or moreinstructions may be, for example, computer executable and/or logicimplemented instructions. In an embodiment, the non-transitory machinereadable media 7002 can include computer readable media 7006. In anembodiment, the non-transitory machine readable media 7002 can includerecordable-type media 7008.

Any of the methods described herein, including, e.g., the methods ofFIGS. 12-19, 22, 25, 28, 30, 32, 34, 40, 42, 45, 48, 50, 52, 54, 56, 58,60, 62, 64, 66, 68 and 70, may be implemented using the devices asdepicted and described herein, e.g., in conjunction with FIGS. 1, 2, 3,4A-4E, 5, 7, 8, 20A-20B, 23A-23D, 26A-26C, 41A-41B, 44 and 47.

The various embodiments described herein may be implemented,individually and/or collectively, by various types of electro-mechanicalsystems having a wide range of electrical components such as hardware,software, firmware, and/or virtually any combination thereof; and a widerange of components that may impart mechanical force or motion such asrigid bodies, spring or torsional bodies, hydraulics,electro-magnetically actuated devices, and/or virtually any combinationthereof. Consequently, as used herein “electro-mechanical system”includes, but is not limited to, electrical circuitry operably coupledwith a transducer (e.g., an actuator, a motor, a piezoelectric crystal,a Micro Electro Mechanical System (MEMS), etc.), electrical circuitryhaving at least one discrete electrical circuit, electrical circuitryhaving at least one integrated circuit, electrical circuitry having atleast one application specific integrated circuit, electrical circuitryforming a general purpose computing device configured by a computerprogram (e.g., a general purpose computer or a microprocessor),electrical circuitry forming a memory device (e.g., forms of memory(e.g., random access, flash, read only, etc.)), electrical circuitryforming a communications device (e.g., a wireless communication device,communications switch, optical-electrical equipment, etc.), and/or anynon-electrical analog thereto, such as optical or other analogs.

The various aspects of the embodiments for methods, processes, apparatusand systems as described herein can be implemented, individually and/orcollectively, by a wide range of hardware, software, firmware, or anycombination thereof. The state of the art has progressed to the pointwhere there is little distinction left between hardware, software,and/or firmware implementations of aspects of systems; the use ofhardware, software, and/or firmware is generally (but not always, inthat in certain contexts the choice between hardware and software canbecome significant) a design choice representing cost vs. efficiencytradeoffs. There are various vehicles by which processes and/or systemsand/or other technologies described herein can be effected (e.g.,hardware, software, and/or firmware), and that the preferred vehiclewill vary with the context in which the processes and/or systems and/orother technologies are deployed. For example, if an implementerdetermines that speed and accuracy are paramount, the implementer mayopt for a mainly hardware and/or firmware vehicle; alternatively, ifflexibility is paramount, the implementer may opt for a mainly softwareimplementation; or, yet again alternatively, the implementer may opt forsome combination of hardware, software, and/or firmware. Hence, thereare several possible vehicles by which the processes and/or devicesand/or other technologies described herein may be effected, none ofwhich is inherently superior to the other in that any vehicle to beutilized is a choice dependent upon the context in which the vehiclewill be deployed and the specific concerns (e.g., speed, flexibility, orpredictability) of the implementer, any of which may vary.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples. Insofar as such block diagrams, flowcharts, and/orexamples contain one or more functions and/or operations, it will beunderstood by those within the art that each function and/or operationwithin such block diagrams, flowcharts, or examples can be implemented,individually and/or collectively, by a wide range of hardware, software,firmware, or virtually any combination thereof. In one embodiment,several portions of the subject matter described herein may beimplemented via Application Specific Integrated Circuits (ASICs), FieldProgrammable Gate Arrays (FPGAs), digital signal processors (DSPs), orother integrated formats. However, some aspects of the embodimentsdisclosed herein, in whole or in part, can be equivalently implementedin integrated circuits, as one or more computer programs running on oneor more computers (e.g., as one or more programs running on one or morecomputer systems), as one or more programs running on one or moreprocessors (e.g., as one or more programs running on one or moremicroprocessors), as firmware, or as virtually any combination thereof,and that designing the circuitry and/or writing the code for thesoftware and or firmware would be well within the skill of one of skillin the art in light of this disclosure. In addition, the mechanisms ofthe subject matter described herein are capable of being distributed asa program product in a variety of forms, and that an illustrativeembodiment of the subject matter described herein applies regardless ofthe particular type of non-transitory machine readable media used toactually carry out the distribution. Examples of a non-transitorymachine readable media include, but are not limited to, the following:non-transitory machine readable media such as a floppy disk, a hard diskdrive, a Compact Disc (CD), a Digital Video Disk (DVD), a digital tape,a computer memory, etc.

The herein described subject matter sometimes illustrates differentcomponents contained within, or connected with, different othercomponents. It is to be understood that such depicted architectures aremerely exemplary, and that in fact many other architectures may beimplemented which achieve the same functionality. In a conceptual sense,any arrangement of components to achieve the same functionality iseffectively “associated” such that the desired functionality isachieved. Hence, any two components herein combined to achieve aparticular functionality can be seen as “associated with” each othersuch that the desired functionality is achieved, irrespective ofarchitectures or intermedial components. Likewise, any two components soassociated can also be viewed as being “operably connected”, or“operably coupled,” to each other to achieve the desired functionality,and any two components capable of being so associated can also be viewedas being “operably couplable,” to each other to achieve the desiredfunctionality. Specific examples of operably couplable include but arenot limited to physically mateable and/or physically interactingcomponents, and/or wirelessly interactable, and/or wirelesslyinteracting components, and/or logically interacting, and/or logicallyinteractable components.

In some instances, one or more components may be referred to herein as“configured to,” “configured by,” “configurable to,” “operable/operativeto,” “adapted/adaptable,” “able to,” “conformable/conformed to,” etc.Those skilled in the art will recognize that such terms (e.g.“configured to”) can generally encompass active-state components and/orinactive-state components and/or standby-state components, unlesscontext requires otherwise.

While particular aspects of the present subject matter described hereinhave been shown and described, it will be apparent to those skilled inthe art that, based upon the teachings herein, changes and modificationsmay be made without departing from the subject matter described hereinand its broader aspects and, therefore, the appended claims are toencompass within their scope all such changes and modifications as arewithin the true spirit and scope of the subject matter described herein.It will be understood by that the reader that, in general, terms usedherein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood that if a specific number of anintroduced claim recitation is intended, such an intent will beexplicitly recited in the claim, and in the absence of such recitationno such intent is present. For example, as an aid to understanding, thefollowing appended claims may contain usage of the introductory phrases“at least one” and “one or more” to introduce claim recitations.However, the use of such phrases should not be construed to imply thatthe introduction of a claim recitation by the indefinite articles “a” or“an” limits any particular claim containing such introduced claimrecitation to claims containing only one such recitation, even when thesame claim includes the introductory phrases “one or more” or “at leastone” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an”should typically be interpreted to mean “at least one” or “one ormore”); the same holds true for the use of definite articles used tointroduce claim recitations. In addition, even if a specific number ofan introduced claim recitation is explicitly recited, such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to “at least one of A, B, and C, etc.” is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., “a system having at least one ofA, B, and C” would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to “at least one of A, B, or C, etc.” is used, ingeneral such a construction is intended as (e.g., “a system having atleast one of A, B, or C” would include but not be limited to systemsthat have A alone, B alone, C alone, A and B together, A and C together,B and C together, and/or A, B, and C together, etc.). Typically adisjunctive word and/or phrase presenting two or more alternative terms,whether in the description, claims, or drawings, should be understood tocontemplate the possibilities of including one of the terms, either ofthe terms, or both terms unless context dictates otherwise. For example,the phrase “A or B” will be typically understood to include thepossibilities of “A” or “B” or “A and B.”

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations are not expressly set forth herein for sakeof clarity.

All of the above U.S. patents, U.S. patent application publications,U.S. patent applications, foreign patents, foreign patent applicationsand non-patent publications referred to in this specification and/orlisted in any Application Data Sheet, are incorporated herein byreference, to the extent not inconsistent herewith.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent. The various aspects andembodiments disclosed herein are for purposes of illustration and arenot intended to be limiting, with the true scope and spirit beingindicated by the following claims.

1. A system comprising: non-transitory machine readable media, for usein a lumen traveling device control system, including: one or moreinstructions that cause the lumen traveling device control system toidentify at least two possible directions of travel of a lumen travelingdevice through a body tube tree, the body tube tree including aplurality of branched, interconnected channels, and the at least twopossible directions of travel corresponding to at least two of thebranched, interconnected channels; one or more instructions that causethe lumen traveling device control system to receive data representing astored parameter value relating to a previous event associated with atleast one of the at least two possible directions of travel; one or moreinstructions that cause the lumen traveling device control system toselect a direction of travel from the at least two directions of travelbased at least in part on the data representing a stored parameter valuerelating to a previous event associated with at least one of the atleast two possible directions of travel; and one or more instructionsthat cause the lumen traveling device control system to direct at leastone of a steering mechanism and a propelling mechanism on the lumentraveling device to cause the lumen traveling device to move through thebody tube tree in the selected direction of travel. 2.-4. (canceled) 5.The system of claim 1, wherein the non-transitory machine readable mediabears one or more instructions that cause the lumen traveling devicecontrol system to determine that at least one of the at least twodirections of travel is non-navigable by the lumen traveling device, andwherein the one or more instructions that cause the lumen travelingdevice control system to select a direction of travel from the at leasttwo directions of travel based at least in part on the data representinga stored parameter value relating to a previous event associated with atleast one of the at least two possible directions of travel includeinstructions that cause the lumen traveling device control system toavoid the at least one of the at least two directions of travel if it isnon-navigable by the lumen traveling device. 6.-11. (canceled)
 12. Thesystem of claim 1, wherein the non-transitory machine readable mediaincludes: one or more instructions that cause the lumen traveling devicecontrol system to identify a stop condition based at least in part onthe data; and one or more instructions that cause the lumen travelingdevice control system to direct at least one of the steering mechanismand the propelling mechanism on the lumen traveling device to cause thelumen traveling device to stop moving through the body tube tree. 13.The system of claim 1, wherein the non-transitory machine readable mediaincludes: one or more instructions that cause the lumen traveling devicecontrol system to store the data in a memory location on the lumentraveling device.
 14. The system of claim 1, wherein the non-transitorymachine readable media includes: one or more instructions that cause thelumen traveling device control system to store the motion controlinstructions for directing operation of at least one of the steeringmechanism and the propelling mechanism in a memory location on the lumentraveling device.
 15. The system of claim 1, wherein the non-transitorymachine readable media includes: one or more instructions that cause thelumen traveling device control system to transmit the data representinga stored parameter value relating to a previous event associated with atleast one of the at least two possible directions of travel from thelumen traveling device to a remote device.
 16. The system of claim 1,wherein the non-transitory machine readable media includes: one or moreinstructions that cause the lumen traveling device control system totransmit motion control instructions for directing operation of at leastone of the steering mechanism and the propelling mechanism from thelumen traveling device to a remote device.
 17. The system of claim 1,wherein the non-transitory machine readable media includes: one or moreinstructions that cause the lumen traveling device control system toreceive at least one of instructions or data from a remote device. 18.The system of claim 1, wherein the non-transitory machine readable mediais carried by the lumen traveling device.
 19. The system of claim 1,wherein the non-transitory machine readable media is carried in part bythe lumen traveling device and in part by a remote device. 20.-22.(canceled)
 23. The system of claim 1, wherein the non-transitory machinereadable media includes: one or more instructions that cause the lumentraveling device control system to receive information related towhether or not at least one of at least two possible directions oftravel of the lumen traveling device through the body tube tree haspreviously been traveled by the lumen traveling device; and one or moreinstructions that cause the lumen traveling device control system toselect a direction of travel from the at least two possible directionsof travel based at least in part on the information related to whetheror not at least one of at least two possible directions of travel of thelumen traveling device through the body tube tree has previously beentraveled by the lumen traveling device.
 24. A method of operating alumen traveling device with a lumen traveling device control system,comprising: identifying at least two possible directions of travel of alumen traveling device through a body tube tree, the body tube treeincluding a plurality of branched, interconnected channels, and the atleast two possible directions of travel corresponding to at least two ofthe branched, interconnected channels; receiving data representing astored parameter value relating to a previous event; selecting adirection of travel from the at least two directions of travel based atleast in part on the data representing a stored parameter value relatingto a previous event; and directing at least one of a steering mechanismand a propelling mechanism on the lumen traveling device to cause thelumen traveling device to move through the body tube tree in theselected direction of travel. 25.-34. (canceled)
 35. The method of claim24, further comprising: identifying a stop condition based at least inpart on the data; and directing at least one of the steering mechanismand the propelling mechanism on the lumen traveling device to cause tocause the lumen traveling device to stop moving through the body tubetree.
 36. The method of claim 24, further comprising: storing the datain a memory location on the lumen traveling device.
 37. The method ofclaim 24, further comprising: storing motion control instructions fordirecting operation of at least one of the steering mechanism and thepropelling mechanism in a memory location on the lumen traveling device.38. The method of claim 24, further comprising: transmitting the datafrom the lumen traveling device to a remote device.
 39. The method ofclaim 24, further comprising: transmitting motion control instructionsfor directing operation of at least one of the steering mechanism andthe propelling mechanism from the lumen traveling device to a remotedevice.
 40. The method of claim 24, further comprising: receiving atleast one of instructions or data from a remote device.
 41. The methodof claim 24, performed under the control of a lumen traveling devicecontrol system on-board the lumen traveling device.
 42. The method ofclaim 24, performed under the control of a lumen traveling devicecontrol system located in part on-board the lumen traveling device andin part on a remote device.
 43. The method of claim 24, furthercomprising: receiving information related to whether or not at least oneof at least two possible directions of travel of the lumen travelingdevice through the body tube tree has previously been traveled by thelumen traveling device; and selecting the direction of travel from theat least two possible directions of travel based at least in part on theinformation related to whether or not at least one of at least twopossible directions of travel of the lumen traveling device through thebody tube tree has previously been traveled by the lumen travelingdevice.
 44. The system of claim 1, wherein the one or more instructionsthat cause the lumen traveling device control system to receive datarepresenting a stored parameter value relating to a previous eventassociated with at least one of the at least two possible directions oftravel include one or more instructions that cause the lumen travelingdevice control system to receive data relating to at least one of aprevious action performed by the lumen traveling device or a parametervalue previously sensed by the lumen traveling device.
 45. The system ofclaim 1, wherein the one or more instructions that cause the lumentraveling device control system to direct at least one of the steeringmechanism and the propelling mechanism on the lumen traveling device tocause the lumen traveling device to move through the body tube tree inthe selected direction of travel include one or more instructions thatcause the lumen traveling device control system to direct at least oneof the steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to move through thebody tube tree in the selected direction of travel for a pre-determineddistance, cause the lumen traveling device to move through the body tubetree in the selected direction of travel for a pre-determined duration,cause the lumen traveling device to move through the body tube tree inthe selected direction of travel until a stop instruction is receivedfrom a remote device by the lumen traveling device, cause the lumentraveling device to turn, cause the lumen traveling device to continuemoving in a current direction of travel, or cause the lumen travelingdevice to reverse its direction of travel.
 46. The system of claim 1,wherein the non-transitory machine readable media includes at least oneof computer readable media, a non-volatile memory in the lumen travelingdevice, ROM, PROM, EPROM, EEPROM, or Flash memory.
 47. The method ofclaim 24, wherein receiving data representing a stored parameter valuerelating to a previous event includes receiving data relating to atleast one of a previous action performed by the lumen traveling deviceor a parameter value previously sensed by the lumen traveling device.48. The method of claim 24, wherein directing at least one of thesteering mechanism and the propelling mechanism on the lumen travelingdevice to cause the lumen traveling device to move through the body tubetree in the selected direction of travel includes directing at least oneof the steering mechanism and the propelling mechanism on the lumentraveling device to cause the lumen traveling device to move through thebody tube tree in the selected direction of travel for a pre-determineddistance, cause the lumen traveling device to move through the body tubetree in the selected direction of travel for a pre-determined duration,cause the lumen traveling device to move through the body tube tree inthe selected direction of travel until an stop instruction is receivedfrom a remote device by the lumen traveling device, cause the lumentraveling device to turn, cause the lumen traveling device to continuemoving in a current direction of travel, or cause the lumen travelingdevice to reverse its direction of travel.